Magnetic Resonance Chemical Shift Imaging Research Articles

Recent advances in noninvasive assessment of liver steatosis.

Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.

Milk intake enhances cerebral antioxidant (glutathione) concentration in older adults: A randomized controlled intervention study.

BackgroundA major antioxidant, glutathione (GSH), is a key factor in the antioxidant defense mechanism against oxidative stress and aging-related functional declines. Our previous observational study showed positive correlations between brain GSH concentrations and dairy food consumption, particularly milk (p < 0.001), in older adults.ObjectiveTo investigate whether a recommended amount of milk intake (3 cups/day) in low dairy consumers enhances brain GSH concentrations through an intervention trial.MethodsSeventy-three older adults (60–89 years) with a low dairy intake (≤1.5 servings/day) were randomized (5:2 ratio) in this 3-month randomized clinical trial. The intervention group was provided 1% milk weekly and instructed to consume 3 cups of milk/day for 3 months while the control group continued their habitual intake of total dairy ≤ 1.5 servings/day (<1 cup of milk/day). Brain GSH concentrations were measured in the fronto-parietal region using our unique 3 T magnetic resonance chemical shift imaging technique at baseline and 3 months.ResultsAmong 73 randomized participants, 66 participants (49 intervention; 17 controls) completed the study. Milk intake in the intervention group increased from 0.2 ± 0.3 cups/day to 3.0 ± 0.6 cups/day (p < 0.001) between baseline and the end of the study, while milk intake in the control group did not differ throughout the study duration (0.4 ± 0.4 cups/day). The intervention group showed increases in brain GSH concentrations by 7.4 ± 11.7% (p < 0.001) in parietal and 4.7 ± 9.8% (p = 0.003) in fronto-parietal regions, and 4.6 ± 8.7% (p < 0.001) in overall brain concentration after the intervention compared with baseline, while the control group showed no changes.ConclusionThis study provides evidence that milk serves as a good dietary source to increase and/or restore brain GSH concentrations in older adults. Identifying dietary sources that effectively enhance antioxidant defenses and neuroprotection could lead to the development of new strategies to promote brain health in the aging population.Clinical trial registration[https://ClinicalTrials.gov], identifier [NCT02957422].

In-Vivo Retention of 5-Fluorouracil Using 19F Magnetic Resonance Chemical Shift Imaging in Colorectal Cancer in a Murine Model

Colorectal cancer is the third leading cause of cancer death worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapies for treatment of solid tumours, including colorectal cancer. The efficacy of treatment is dependent on tumour type and can only be determined six weeks after beginning chemotherapy, with only 40–50% of patients responding positively to the 5-FU therapy. In this paper, we demonstrate the potential of using Magnetic Resonance (MR) Chemical Shift Imaging (CSI) for in-vivo monitoring of 5-FU tumor-retention in two different colorectal tumour types (HT-29 & H-508). Time curves for 5-FU signals from the liver and bladder were also acquired. We observed significant differences (p < 0.01) in 5-FU signal time dependencies for the HT-29 and H-508 tumours. Retention of 5-FU occurred in the H-508 tumour, whereas the HT-29 tumour is not expected to retain 5FU due to the observation of the negative b time constant indicating a decline in 5FU within the tumour. This study successfully demonstrates that CSI may be a useful tool for early identification of 5-FU responsive tumours based on observed tumour retention of the 5-FU.

(Invited) NMR Studies of Li Metal Dendrite Formation and Coatings

All solid-state batteries (ASSBs) potentially offer safe electrochemical energy storage as they do not require the liquid organic electrolyte. However, in order to achieve high energy densities that are competitive with conventional lithium ion cells, Li metal anodes are required. Even when nominally pin-hole free ceramic membranes are used, issues surrounding Li microstructural growth and subsequent cell death persist, particularly at high current densities. The use of 7Li magnetic resonance chemical shift imaging to track Li microstructural growth in solid electrolytes will be discussed in this talk. Applications to garnet solid-electrolyte will be described. We follow the early stages of Li microstructural growth during electrochemical cycling – from the formation of Li on the electrode surface to dendritic Li connecting both electrodes in a symmetrical cell and correlate these changes with electrochemistry (e.g. short circuiting). At low current densities, 7Li MRI detects the formation of Li microstructures in cells before obvious electrochemical signatures indicating their presence are observed.

7li Chemical Shift Imaging to Detect Microstructural Growth in All Solid-State Batteries

All solid-state batteries potentially offer safe, high energy density electrochemical energy storage, yet are plagued with issues surrounding Li microstructural growth and subsequent cell death. We use 7Li magnetic resonance chemical shift imaging and electron microscopy to track Li microstructural growth in the garnet solid-electrolyte, Li6.5La3Zr1.5Ta0.5O12. Here, we follow the early stages of Li microstructural growth during electrochemical cycling – from the formation of Li on the electrode surface to dendritic Li connecting both electrodes in a symmetrical cell and correlate these changes with electrochemistry (e.g. short circuiting). During these experiments, we observe changes at both the stripping and plating interfaces during Li microstructural growth, indicating heterogeneities in both Li removal and deposition. At low current densities, 7Li MRI detects the formation of Li microstructures in cells before obvious electrochemical signatures indicating their presence are observed.

MRI chemical shift imaging of the fat content of the pancreas and liver of patients with type 2 diabetes mellitus.

The present study aimed to investigate the association between the content and distribution of fat in the pancreas and liver in patients with type 2 diabetes mellitus (T2DM). A total of 70 patients newly diagnosed with T2DM (T2DM group) and 30 healthy volunteers (normal control group) were enrolled in the present study. Dual-echo magnetic resonance (MR) chemical shift imaging was used to measure the fat content of the liver and the head, body and tail regions of the pancreas. In addition, the distribution of fat in the various regions of the pancreas, as well as the average fat content of the pancreas versus the liver, were compared. The fat content of the pancreatic head, body and tail regions of the T2DM group were 5.59±4.70, 4.80±3.75 and 4.89±3.86%, respectively. The fat content of these regions in the normal control group were 3.89±2.47, 3.30±2.11 and 3.23±2.23%, respectively. The average fat content of the pancreas was 5.19±3.75% for the T2DM group and 3.47±2.00% for the normal control group. The average fat content of the liver was 9.87±3.19% for the T2DM group and 7.24±2.38% for the normal control group. Therefore, the results from MR chemical shift imaging suggested that there were no significant differences in the distribution of fat between the pancreas of patients newly diagnosed with T2DM and that from the healthy population; however, the average fat content in the pancreas of the T2DM group was significantly higher (F=3.597; P<0.05), as compared with the normal control group. In addition, there was no correlation between the fat contents in the pancreas and liver in patients newly diagnosed with T2DM and the healthy population.

Accurate metabolic images of the human myocardium by means of 31P magnetic resonance chemical shift imaging with spatial saturation pulses

The aim of this study was to demonstrate that acquisition‐weighted 31P magnetic resonance spectroscopy with spatial saturation allows for generation of metabolite maps showing the distribution of 31P metabolites, such as phosphocreatine (PCr) and adenosine triphosphate (ATP) in the human myocardium. The method presented here allowed for a considerable shortening of the normally complicated and time‐consuming post‐processing. All examinations were performed on a 1.5 T scanner. Contamination from adjacent organs to the myocardial signal was suppressed using spatial saturation pulses and an acquisition‐weighted sampling scheme. All measurements were ECG‐triggered and performed in prone position. Both healthy subjects and patients with infarcted myocardium were examined. For comparison of the spectroscopic findings to a conventional technique, the infarcted myocardium was additionally examined with a late‐enhancement technique. The distribution of PCr of the whole left ventricular myocardium could be determined both in healthy subjects and in patients. The measured distribution of PCr in the infarcted myocardium revealed an obvious reduction of signal in the infarcted area, whereas the distributions of the metabolites in healthy myocardium reflected no discontinuities. The study could demonstrate that the application of spatial saturation pulses facilitates the visual representation of 31P metabolites with a post‐processing procedure easy to apply. © 2014 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 187–195, 2013.

3D cardiac Chemical Shift Imaging of [1-13C] hyperpolarized acetate and pyruvate in pigs

Background 13C Dynamic Nuclear Polarization (DNP) with rapid dissolution together with Magnetic Resonance Chemical Shift Imaging (CSI) have been used for non-invasive real-time metabolic assessment in cardiac experimental models on a clinical 3T scanner. Here, we report an in vivo comparison of hyperpolarized [1-13C] pyruvate and [1-13C] acetate perfusion and metabolism: a method based on a 3D Spiral CSI sequence is presented for obtaining spatially and spectrally-resolved information on whole heart cardiac metabolism.

Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T

Background: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. Objective: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. Methods: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4 ± 7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. Results: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p = 0.001). Conclusion: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

Non-invasive diagnostic of cardiac allograft vasculopathy by 31P magnetic resonance chemical shift imaging☆

Coronary angiography is still the gold standard for the diagnosis of cardiac allograft vasculopathy (CAV) for which alternative non-invasive diagnostic approaches are currently investigated. In this study, we assessed whether 31P magnetic resonance chemical shift imaging can diagnose CAV by studying variations in cardiac high-energy phosphates in a population of adult heart transplant recipients. CAV was defined by coronary angiography as the presence of diffuse coronary irregularities with significant concentric narrowing on epicardial or distal coronary arteries. Eight patients with CAV (group A), and 18 patients without CAV (group B) were included in this study and compared to nine healthy volunteers (group C). Patients and volunteers underwent 31P three-dimensional chemical shift imaging to determine the ratio of phosphocreatine (PCr) and adenosine tri-phosphate (ATP). PCr/ATP was significantly lower in group A (1.51+/-0.50) than in groups B and C (1.98+/-0.53 (p=0.003) and 2.14+/-0.31 (p=0.001)), respectively. Time from transplant, number of episodes of acute rejection, and left ventricular ejection fraction (LVEF) were not significantly different between patient groups. A PCr/ATP value of 1.59 was the optimal cut-off value to predict CAV (specificity and sensitivity of 100% and 72%, respectively). Clinically, in vivo 31P chemical shift imaging is a promising, non-invasive method to detect the potential modifications of high-energy phosphates related to CAV and to better screen indications for coronary angiograms. This may be relevant for coronary angiography follow-up and adjustments of immunotherapy regimen.

Microscopic images of intraspheroidal pH by 1H magnetic resonance chemical shift imaging of pH sensitive indicators

We investigate microscopic pH heterogeneity within tumor spheroids using a novel 1H NMR methodology that provides high resolution measurements of intraspheroidal pH. High resolution microscopic images of intraspheroidal pH were obtained by 1H NMR using chemical shift selective excitation of the H2 resonance of imidazole added to the incubation medium. Imidazole accumulated in the intraspheroidal space in a pH dependent manner. Maps of intraspheroidal pH could be obtained by transforming pixel by pixel (32 x 32 micro) the regional variation of imidazole H2 intensity into a relative pH scale. Our analysis revealed drastic intraspheroidal pH alterations depending on the size of the spheroid, ca. 0.6 pH units more acidic in the necrotic core than in the periphery, for spheroids of 600 mum diameter. The presence of concentric regions having similar intraspheroidal pH was consistently observed. The thickness of these regions decreased from pH 7.2 to pH 6.8 and increased below the latter pH value. Our observations are compatible with the general model of spheroid growth where the more external layers of cells are in active growth and depict more alkaline pH values while the inner layers remain quiescent or evolve to a necrotic core, depicting more acidic pH values.

Nonnegative Matrix Factorization for Rapid Recovery of Constituent Spectra in Magnetic Resonance Chemical Shift Imaging of the Brain

We present an algorithm for blindly recovering constituent source spectra from magnetic resonance (MR) chemical shift imaging (CSI) of the human brain. The algorithm, which we call constrained nonnegative matrix factorization (cNMF), does not enforce independence or sparsity, instead only requiring the source and mixing matrices to be nonnegative. It is based on the nonnegative matrix factorization (NMF) algorithm, extending it to include a constraint on the positivity of the amplitudes of the recovered spectra. This constraint enables recovery of physically meaningful spectra even in the presence of noise that causes a significant number of the observation amplitudes to be negative. We demonstrate and characterize the algorithm's performance using 31P volumetric brain data, comparing the results with two different blind source separation methods: Bayesian spectral decomposition (BSD) and nonnegative sparse coding (NNSC). We then incorporate the cNMF algorithm into a hierarchical decomposition framework, showing that it can be used to recover tissue-specific spectra given a processing hierarchy that proceeds coarse-to-fine. We demonstrate the hierarchical procedure on 1H brain data and conclude that the computational efficiency of the algorithm makes it well-suited for use in diagnostic work-up.

Prediction of Treatment Response of Head and Neck Cancers with P-31 MR Spectroscopy from Pretreatment Relative Phosphomonoester Levels

Rationale and Objectives Combinations of chemotherapy and fractionated radiation therapy are the currently preferred nonsurgical treatment methods for squamous cell carcinoma of the head and neck, but to the authors' knowledge there is no reliable marker for predicting therapeutic response. Early identification of nonresponders would allow prompt replacement of ineffective, toxic therapy by alternative, potentially more effective procedures. Frequent regional node involvement facilitates surface coil investigation with phosphorus-31 magnetic resonance spectroscopy. Materials and Methods P-31 magnetic resonance spectra were acquired from 12 patients before radiation therapy or chemotherapy. In vivo three-dimensional localized P-31 nuclear magnetic resonance chemical shift imaging was performed with a 1.5-T clinical imager and a dual-tuned H-1/P-31 surface coil. Proton decoupling and nuclear Overhauser enhancement were used to improve sensitivity and resolve overlapping signals in the phosphomonoester region of the spectrum. Results The average pretreatment ratio of phosphomonoester to β-nucleoside triphosphate was significantly smaller in complete responders ( n = 4) than in incomplete responders (partial responders plus nonresponders, n = 8) (0.0 ± 0.0 vs 1.22 ± 0.17 [ P = .004]). Conclusion Results of this preliminary study suggest that H-1–decoupled P-31 magnetic resonance spectroscopy may prove to be a useful predictor of therapeutic response in head and neck cancers.

Magnetic resonance chemical shift microimaging of aging human skin in vivo: initial findings.

In recent decades, interest has increased in the chronological and environmental factors governing the aging of skin. Various methods have been used for determining water and lipid content of human skin as a function of subject age. Magnetic resonance chemical shift imaging (CSI) offers a noninvasive technique for observing detailed distributions of water, lipids and other chemicals in the skin, and thus may be useful in dermatogerontology. Human skin was examined in vivo on nine healthy volunteers, both male and female. Localized (1) H spectra of the skin were obtained from voxels 78 μm thick and parallel to the skin surface. Unique water and lipid profiles were observed for different individuals, showing the composition and microstructure of epidermis, dermis and hypodermis in each subject. These allowed the quantification of skin thickness in vivo by the first appearance of triacylglyceride olefinic protons at the dermal-hy-podermal junction, or alternatively by the degree of lipid infiltration into dermis. The relative concentration of free water in the skin, normalized to skin thickness, was observed to be slightly greater in older subjects and also in tanned subjects. More significantly, a microstructural feature common to every subject, i.e., the position of a possible capillary plexus in the dermis, showed migration toward the skin surface with advancing age. Such observations are consistent with previous studies of skin aging by other techniques and show promise for CSI in dermatogerontology as a non-invasive means for determination of skin water in vivo.

Theoretical Evaluation and Comparison of Fast Chemical Shift Imaging Methods

Magnetic resonance chemical shift imaging (CSI) is becoming the method of choice for localized NMR spectroscopic examinations, allowing simultaneous detection of NMR spectra from a large number of voxels. The main limitation of these methods is their long experimental duration. A number of fast CSI experiments have been presented, promising to reduce that duration. In this contribution the criteria for evaluating and optimizing the sensitivity of fast CSI experiments are elaborated. For a typical experiment in the human brain, the performance of various methods is compared. While conventional CSI provides optimal sensitivity per unit time, it is shown in which circumstances fast sequences allow a shorter experimental duration. Using these results, the best method for any experimental requirements can be selected.

Lactate and pH mapping in calf muscles of rats during ischemia/reperfusion assessed by in vivo proton and phosphorus magnetic resonance chemical shift imaging.

Metabolic images of phosphocreatine, inorganic phosphate (Pi), and pH formed by phosphorus 31 (31P) nuclear magnetic resonance (NMR) spectroscopy, that of lactate by proton (1H) NMR spectroscopy and 1H magnetic resonance imaging (MRI) were concurrently observed using the same ischemia/reperfusion model in the calf muscles of rats. From the multidimensional analyses, the correlation between tissue pH and lactate formation was examined. Six rats were used in the study. For the selective detection of lactate by 1H NMR, a multiple quantum coherence filter was used. The localization of the metabolites and pH was achieved by three-dimensional chemical shift imaging technique. These observations were repeated in 1-hour cycles during 6 hours of ischemia and after reperfusion. The tibialis anterior and gastrocnemius muscles, which are mainly composed of fast-twitch muscle fibers, showed severe tissue edema and irreversible phosphoenergetic change. These muscles became more acidic than other portions of the calf. In contrast, the central part of the calf including soleus muscle (slow-twitch muscle) showed reversible phosphoenergetic changes. Lactate accumulated mainly between the muscles showing reversible and irreversible phospho-energetic changes. Discrepancy between acidosis and lactate accumulation in calf muscles was observed in this ischemia/reperfusion model, although the exact reasons for this phenomenon could not be explained by this study.

Heterogeneous Metabolic Changes in the Calf Muscle of the Rat during Ischaemia-reperfusion: in Vivo Analysis by 31P Nuclear Magnetic Resonance Chemical Shift Imaging and 1H Magnetic Resonance Imaging

Non-localized and localized 31P nuclear magnetic resonance (NMR) spectra of rat calf muscle during arterial occlusion and after reperfusion were concurrently observed using chemical shift imaging and ‘H magnetic resonance imaging (MRI). During ischaemia. the levels of high-energy phosphates (phosphocreatine and adenosine 5′-triphosphate) were depleted and that of inorganic phosphate was increased. In addition, the signal intensity on 1H MRI was increased. These changes were observed to be relatively homogeneous throughout the calf. In contrast, the changes during reperfusion were heterogeneous. In the central part of the calf, inorganic phosphate disappeared, phosphocreatine was restored immediately on reperfusion and the ‘H signal was decreased. However, in the regions of the tibialis anterior muscle and the superficial part of the gastrocnemius muscle, inorganic phosphate persisted for several hours, phosphocreatine was not restored and the signal intensity on T2-weighted 1H MRI was increased further. The heterogeneous changes detected by 31P NMR spectroscopy and 1H MRI showed close agreement. The susceptibility of different calf muscles to ischaemia and reperfusion seems to depend on their predominant muscle fibre type (i.e. fast-twitch or slow-twitch fibres). Reversible and irreversible ischaemic changes could be non-invasively distinguished by in vivo31P NMR spectroscopy and 1H MRI.

Magnetic Resonance Chemical Shift Imaging and Spectroscopy of Atherosclerotic Plaque

An in vivo magnetic resonance imaging (MRI) technique for identification and characterization of atherosclerotic plaque was assessed in animal and human models. Atherosclerosis was induced in the abdominal aorta of four rabbits by a combination of balloon denudation and a high cholesterol diet. In vivo conventional spin-echo and fat/water suppressed images of the rabbit aortae were obtained at 1.5 T. Chemical shift imaging (CSI) was achieved using a hybridization of selective excitation and modified Dixon techniques. These techniques were then used to obtain images of atherosclerotic lesions in the carotid arteries of four patients prior to endarterectomy. The MRI results were corroborated by histologic and high-resolution proton MR spectroscopic (8.5 T) analysis of rabbit aorta, human carotid endarterectomy, and six additional human superficial femoral and iliac atherectomy specimens. All animal and human lesions were classified as either fatty streaks or fibrotic plaque. When compared to conventional spin-echo images, fat suppression by CSI substantially improved the measured contrast-to-noise ratio between plaque and vessel lumen, and enhanced its discrimination from periadventitial fat. In contrast, water suppression eliminated visualization of plaque due to the negligible amount of isotropic (liquid-like) signal from the immobilized lesion lipids. Magnetic resonance spectroscopy corroborated the CSI results by demonstrating broad, ill-defined fat resonances characteristic of nonmobile lipids in both human and rabbit atherosclerotic lesions. These findings indicate that in vivo MRI of plaque is technically feasible and can be markedly improved using chemical shift imaging.

In vivo nuclear magnetic resonance chemical shift imaging by selective irradiation.

NMR images of preselected chemically shifted species can be obtained by selective irradiation of the remainder of the NMR chemical shift spectrum prior to application of a conventional NMR imaging sequence. The chemical-selective irradiation consists of narrow-bandwidth pi/2 or saturation radio-frequency pulses applied in the absence of imaging gradients. The technique permits substantial reductions in scan and reconstruction times over standard three- and four-dimensional Fourier transform chemical-shift-imaging methods, when images of few spectral peaks are desired. It is also suitable for the elimination of chemical shift artifacts in conventional high-field NMR imaging. In vivo applications of the technique to the head and limbs in a 1.5-T magnetic field yield 1H H2O and -CH2-images, with little detectable -CH2- in muscle and brain.

Histochemical, biochemical, and contractile properties of red, white, and intermediate fibers.

Histochemical, biochemical, and contractile properties of red, white, and intermediate fibers.