Search

Summary: Introduction: Insulin resistance (IR) is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has been associated with worse long-term survival and more frequent occurrence of chronic kidney disease (CKD) than in patients without NAFLD. The aim of our study was to evaluate the impact of NAFLD and IR on survival and renal function in patients after liver transplantation (LT). Methods: Our prospective study included 96 LT candidates who were observed after LT. We evaluated patient survival and occurrence of CKD (defined as estimated glomerular filtration [eGFR] ≤1.00 mL/s/1.73 m2 or overt proteinuria) 5 years after LT and at the end of follow-up. Clinical, laboratory, MR and elastographic evaluation before and 1 year after LT were performed as well as liver biopsy 1 year after LT. Results: Of the factors present 1 year after LT, higher ALT (P = 0.021), ALP (P = 0.012) and everolimus treatment (P = 0.025) increased the risk of death at the end of follow-up, borderline significance was found also for higher waist circumference (P = 0.058), AST (P = 0.059), HOMA-IR (P = 0.056) and presence of fibrosis stage ≥3 in biopsy (P = 0.055). In addition to the presence of CKD 1 year after LT (P

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (

Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.

To evaluate cerebral hemodynamic, metabolic and anatomic changes occurring in patients with unilateral occlusion of the internal carotid artery (ICA). Twenty-two patients with unilateral occlusion of ICA and twenty age and sex matched healthy subjects were included in the study. Single voxel proton magnetic resonance spectroscopy (1H-MRS) of the centrum semiovale, semi-automated hippocampal volumetry in T1-weighted scans and transcranial Doppler examination (TCD) with calculation of Breath Holding Index (BHI) were performed in both groups. Metabolic, anatomic, and hemodynamic features were compared between the two groups. The N-acetylaspartate (NAA)/choline (Cho) ratio was significantly lower in both hemispheres of enrolled patients compared to controls (p = 0.005 for the side with occlusion, p = 0.04 for the side without occlusion). The hippocampus volume was significantly reduced bilaterally in patients compared to healthy subjects (p = 0.049). A statistically significant difference in BHI values was observed between the side with occlusion and without occlusion (p = 0.037) of the patients, as well as between BHI values of the side with occlusion and healthy volunteers (p = 0.014). Patients with unilateral ICA occlusion have reduced NAA/Cho ratio in the white matter of both hemispheres and have bilateral atrophy of hippocampus. The alteration of hemodynamics alone cannot explain these changes.

BACKGROUND In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T2 -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied. PURPOSE To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology. STUDY TYPE Cross-sectional. POPULATION/SUBJECTS Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls. FIELD STRENGTH/SEQUENCE 3.0T: susceptibility, T2 *, T2 , T1 relaxometry; 1.5T: T2 , T1 relaxometry. ASSESSMENT The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T2 *, T2 , and T1 relaxation times were calculated for each ROI. STATISTICAL TESTS The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P

Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses.

Uvod : Insulinova resistence (IR) ma velký význam v patogenezi nealkoholove tukove nemoci jater (NAFLD) a dalsich onemocněni. Udaje o prevalenci a vývoji IR u pacientů před a po transplantaci jater (LT) jsou omezene. Cilem nasi prospektivni studie bylo zhodnoceni prevalence a vývoje IR u pacientů před a v prvnich 2 letech po LT. Metody : U 77 pacientů zařazených na cekaci listinu k LT v obdobi 5/2015 až 4/2017 bylo před LT, 6M, 1R a 2R po LT provedeno klinicke a laboratorni vysetřeni a elastografie jater, 1 H MR spektroskopii byl stanoven obsah tuku v jatrech. V 1 a 2 letech po LT byla provedena necilena biopsie jater. Výsledky : IR definovanou jako HOMA-IR ≥ 3,0 mělo 26 pacientů (41,3 %) před LT, 16 pacientů (25,4 %) v 6M po LT, 22 pacientů (34,9 %) v 1R po LT a 29 pacientů (46,0 %) v 2R po LT (p=0,028 pro 2R vs 6M). Předtransplantacni IR korelovala s věkem, indikaci k LT a přitomnosti metabolickeho syndromu. IR hodnocena 2R po LT korelovala s přitomnosti metabolickeho syndromu, hypertenze, diabetu, BMI, GGT, s množstvim jaterniho tuku hodnoceným histologicky i 1 H MR spektroskopii, se stupněm balonove degenerace v biopsii a se stupněm fibrozy dle shear wave elastografie. Zavěr : Prevalence insulinove resistence je vysoka u pacientů před i po LT, významně stoupa s rostouci dobou od LT. Výskytu potransplantacni IR a souvisejicich faktorů je třeba věnovat maximalni peci.

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ((31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO2). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO2 as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO2 increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO2 on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

Magnetic Resonance (MR) compatible ergometers are specialized ergometers used inside the MR scanners for the characterization of tissue metabolism changes during physical stress. They are most commonly used for dynamic phosphorous magnetic resonance spectroscopy (31P MRS), but can also be used for lactate production measurements, perfusion studies using arterial spin labelling or muscle oxygenation measurements by blood oxygen dependent contrast sequences. We will primarily discuss the importance of ergometers in the context of dynamic 31P MRS. Dynamic 31P MRS can monitor muscle fatigue and energy reserve during muscle contractions as well as the dynamics of recuperation of skeletal muscle tissue during the following recovery through signal changes of phosphocreatine (PCr), inorganic phosphate and adenosine triphosphate (ATP). Based on the measured data it is possible to calculate intracellular pH, metabolic flux of ATP through creatine-kinase reaction, anaerobic glycolysis and oxidative phosphorylation and other metabolic parameters as mitochondrial capacity. This review primarily focuses on describing various technical designs of MR compatible ergometers for dynamic 31P MRS that must be constructed with respect to the presence of magnetic field. It is also expected that the construction of ergometers will be easy for the handling and well accepted by examined subjects.

Background Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. Purpose To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. Study type Prospective technical development. Population Three oils with different n-3 FA content and 24 healthy subjects. Field strength/sequence Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. Assessment Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. Statistical tests SVS data were compared to gas chromatography with the Pearson correlation coefficient. Results T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). Data conclusion PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. Level of evidence 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.

19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

An unknown intense signal (Pun ) with a mean chemical shift of 5.3 ppm was observed in 31 P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m2 ) and 12 age-matched healthy controls were examined by (dynamic) 31 P MRS (3 T system, 31 P/1 H coil). Phantoms (glucose-1-phosphate, Pi and PCr) were measured at pH values of 7.05 and 7.51. At rest, Pun signals with intensities higher than 50% of the Pi intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the Pun signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra- and intracellular alkaline phosphate pools. 2,3-diphosphoglycerate and glucose-1-phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3-diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose-1-phosphate because its chemical shifts are about 0.2 ppm downfield from the Pi signal (4.9 ppm). If the Pun signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of Pi in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the Pun signal probably originates from interstitia. Our data suggest that the increased Pun signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

Purpose Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. Procedures One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. Results Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. Conclusions We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo. Electronic supplementary material The online version of this article (10.1007/s11307-018-1270-3) contains supplementary material, which is available to authorized users.

The standard method for assessment of effect of revascularization in patients with diabetic foot (DF) and critical limb ischemia (CLI) is transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could be impaired in patients with diabetes and its complications. The aim of our study was to compare MRS of calf muscle between patients with DF and CLI and healthy controls and to evaluate the contribution of MRS in the assessment of the effect of revascularization.Thirty-four diabetic patients with DF and CLI treated either by autologous cell therapy (ACT; 15 patients) or percutaneous transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016 and 19 healthy controls were included into the study. TcPO2 measurement was used as a standard method of non-invasive evaluation of limb ischemia. MRS examinations were performed using the whole-body 3T MR system 1 day before and 3 months after the procedure. Subjects were examined in a supine position with the coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and during the exercise period. Rest MRS parameters of oxidative muscle metabolism such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE), adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant PCr (τPCr) and mitochondrial capacity (Qmax), and pH were compared between patients and healthy controls, and also before and 3 months after revascularization.Patients with CLI had significantly lower PCr/Pi (p0.001), significantly higher Pi and pH (both p0.01), significantly lower Qmax and prolonged τPCr (both p0.001) in comparison with healthy controls. We observed a significant improvement in TcPO2 at 3 months after revascularization (from 26.4 ± 11.7 to 39.7 ± 17.7 mm Hg, p0.005). However, the rest MRS parameters did not change significantly after revascularization. In individual cases we observed improvement of dynamic MRS parameters. There was no correlation between MRS parameters and TcPO2 values.Results of our study show impaired oxidative metabolism of calf muscles in patients with CLI in comparison with healthy controls. We observed an improvement in dynamic MRS parameters in individual cases; this finding should be verified in a large number of patients during longer follow-up.Key words: autologous cell therapy - critical limb ischemia - diabetic foot - MR spectroscopy.

Disturbances of the gamma-aminobutyric-acid (GABA) system have been suspected of contributing to the pathophysiology of progressive supranuclear palsy (PSP). The ability to rapidly resolve competitive action decisions, such as shifting the gaze to one particular stimulus rather than another, can be predicted by the concentration of GABA in the region of the frontal cortex relevant to eye movements. For this reason, our study measured GABA levels in seven PSP patients and eight healthy controls, using proton magnetic resonance spectroscopy, and assessed the relationship of these measurements to the remote distractor effect (RDE), an eye-movement paradigm investigating competitive action decisions. No significant differences were found in either frontal-eye-field GABA levels or RDE between PSP patients and controls.

Subcutaneously implanted polymeric scaffolds represent an alternative transplantation site for pancreatic islets (PIs) with the option of vascularisation enhancement by mesenchymal stem cells (MSC). Nevertheless, a proper timing of the transplantation steps is crucial. In this study, scaffolds supplemented with plastic rods were implanted into diabetic rats and two timing schemes for subsequent transplantation of bioluminescent PIs (4 or 7 days after rod removal) were examined by multimodal imaging. The cavities were left to heal spontaneously or with 10 million injected MSCs. Morphological and vascularisation changes were examined by MRI, while the localisation and viability of transplanted islets were monitored by bioluminescence imaging. The results show that PIs transplanted 4 days after rod removal showed the higher optical signal and vascularisation compared to transplantation after 7 days. MSCs slightly improved vascularisation of the graft but hindered therapeutic efficiency of PIs. Long-term glycaemia normalisation (4 months) was attained in 80% of animals. In summary, multimodal imaging confirmed the long-term survival and function of transplanted PIs in the devices. The best outcome was reached with PIs transplanted on day 4 after rod removal and therefore the suggested protocol holds a potential for further applications.

The effects of aging, magnetic field and the voxel localization on measured concentrations of citrate (Cit), creatine (Cr), cholines (Cho) and polyamines (PA) in a healthy prostate were evaluated. 36 examinations at both 1.5T and 3T imagers of 52 healthy subjects aged 19–71 years were performed with PRESS 3D-CSI sequences (TE = 120 and 145 ms). Concentrations in laboratory units and their ratios to citrate were calculated using the LCModel technique. Absolute concentrations were also obtained after the application of correction coefficients. Statistical analysis was performed using a robust linear mixed effects model. Significant effects of aging, the magnetic field strength and the voxel position in central (CZ) or peripheral (PZ) zones on all measured metabolites were found. The concentrations (mmol/kg wet tissue) including prediction intervals in a range of 20–70 years were found: Cit: 7.9–17.2; Cho: 1.4–1.7; Cr: 2.8-2.5; PA (as spermine): 0.6–2.1 at 3T in CZ. In PZ, the concentrations were higher by about 10 % as compared to CZ. Increasing citrate and spermine concentrations with age are significant and correlate well with a recently described increase of zinc in the prostate. These findings should be considered in decision-making if the values obtained from a subject are in the range of control values.

Huntington’s disease (HD) is an inherited autosomal neurodegenerative disorder affecting predominantly the brain, characterized by motor dysfunctions, behavioral and cognitive disturbances. The aim of this study was to determine changes in the brain of transgenic minipigs before HD onset using 1H magnetic resonance (MR) spectroscopy. Measurements were performed on a 3 T MR scanner using a single voxel spectroscopy sequence for spectra acquisition in the white matter and chemical shift imaging sequence for measurement in the striatum, hippocampus and thalamus. A decrease of (phospho)creatine (tCr) concentration was found only in the thalamus (p=0.002) of transgenic minipigs, nevertheless we found significant changes in metabolite ratios. Increase of the ratio choline compounds (tCho)/tCr was found in all examined areas: striatum (p=0.010), thalamus (p=0.011) as well as hippocampus (p=0.027). The ratio N-acetylaspartate+N-acetylaspartylglutamate (tNAA)/tCr (p=0.043) and glutamate+glutamine (Glx)/tCr (p=0.039) was elevated in the thalamus, the ratio myo-inositol (Ins)/tCr (p=0.048) was significantly increased in the hippocampus. No significant differences were observed in the metabolite concentrations in the white matter, however we found significant increase of ratios tNAA/tCr (p=0.018) and tCho/tCr (p=0.003) ratios in transgenic boars. We suppose that the majority of the observed changes are predominantly related to changes in energy metabolism caused by decrease of tCr.

Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.

The myocardium examination by MR spectroscopy is very challenging due to movements caused by the cardiac rhythm and breathing. The aim of the study was to investigate the influence of breathing on the quantitative measurement of lipid/water ratios in different groups of volunteers and different measuring protocols. We examined the lipid content of myocardium at 3T using the proton single voxel spectroscopy. Three protocols (free breathing, breath hold and the use of respiratory navigator) controlled by ECG were used for the examination of 42 adult volunteers including 14 free divers. Spectra were evaluated using jMRUI software. An average content of lipids in the healthy interventricular septum, gained by all protocols was equal to 0.6 %, which is in agreement with other published data. Based on the quality of examinations and the highest technical success, the best protocol seems to be the one containing a respiratory navigator since it is more acceptable by patients. Based on our results and the literature data we can conclude that MR spectroscopy is able to distinguish patients from controls only if their myocardial lipid content is higher than 1.6 % (mean value of lipids plus two standard deviations).

Background Omega‐3 (n‐3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n‐3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. Purpose To detect omega‐3 (n‐3 CH3) and non‐omega‐3 (CH3) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n‐3 FA content, and the n‐3 FA fraction in adipose tissue in vivo. Study Type Prospective technical development. Population Three oils with different n‐3 FA content and 24 healthy subjects. Field Strength/Sequence Single‐voxel MR spectroscopy (SVS) with a point‐resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. Assessment Knowledge about the J‐coupling evolution of both CH3 resonances was used for the optimal detection of the n‐3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. Statistical Tests SVS data were compared to gas chromatography with the Pearson correlation coefficient. Results T2 relaxation times in oils were assessed as follows: CH2, 65 ± 22 msec; CH3, 325 ± 7 msec; and n‐3 CH3, 628 ± 34 msec. The n‐3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). Data Conclusion PRESS with ultralong‐TE can detect and quantify the n‐3 CH3 signal in vivo at 7 T. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71–82.

BACKGROUND Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). OBJECTIVES We therefore explored how the administration of high-fat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1H-MRS) in healthy subjects. METHODS Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m2] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. RESULTS HFC increased to 119 ± 19% (P

Background: Heart failure (HF) is often associated with iron deficiency (ID). Skeletal muscle abnormalities are common in HF, but the potential role of ID in this phenomenon is unclear. In addition to hemopoiesis, iron is essential for muscle bioenergetics. We examined whether energetic abnormalities in skeletal muscle in HF are affected by ID and if they are responsive to intravenous iron. Methods and Results: Forty-four chronic HF subjects and 25 similar healthy volunteers underwent 31 P magnetic resonance spectroscopy of calf muscle at rest and during exercise (plantar flexions). Results were compared between HF subjects with or without ID. In 13 ID-HF subjects, examinations were repeated 1 month after intravenous ferric carboxymaltose administration (1000 mg). As compared with controls, HF subjects displayed lower resting high-energy phosphate content, lower exercise pH, and slower postexercise PCr recovery. Compared with non-ID HF, ID-HF subjects had lower muscle strength, larger PCr depletion, and more profound intracellular acidosis with exercise, consistent with an earlier metabolic shift to anaerobic glycolysis. The exercise-induced PCr drop strongly correlated with pH change in HF group ( r =−0.71, P r =0.13, P =0.61, interaction: P Conclusions: HF patients display skeletal muscle myopathy that is more severe in those with iron deficiency. The presence of ID is associated with greater acidosis with exercise, which may explain early muscle fatigue. Further study is warranted to identify the strategy to restore iron content in skeletal muscle.

Objective 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. Methods Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. Results 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. Conclusion DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

Background 31P-MR spectroscopy is a technique for undertaking a comprehensive evaluation of muscle metabolism. The goal of this study was to compare patients with mild and severe lower limb ischemia measured by 31P-MR spectroscopy at rest and during exercise. Methods Sixteen non-diabetic mild peripheral arterial occlusive disease (PAOD) patients, 23 diabetic PAOD patients with severe ischemia and 19 healthy controls were examined by rest and dynamic 31P-MR spectroscopy with a 3T MR system equipped with an MR-compatible home-made pedal ergometer. Signal intensity ratios of phosphorous metabolites to the sum of all 31P intensities (Ptot) and pH were obtained at rest. The PCr drop (ΔPCr), time recovery constant of PCr (τPCr), pH at the end of the exercise (pHend), and mitochondrial capacity (Qmax) were calculated from dynamic MR spectra. Results Diabetic PAOD patients with severe ischemia differed from controls in both rest (PCr/Pi, βATP/Ptot, pH) and dynamic (Qmax, pHend, τPCr) parameters. PAOD patients with mild ischemia differed from controls only in Qmax and pHend. Rest parameters of the nondiabetic PAOD patients did not differ from control values excluding rest pH which was higher in both patient groups. Conclusions A combination of rest and dynamic 31P-MR spectroscopy can distinguish among all three groups of subjects. On the other hand, examination at rest is sufficient for differentiation between patient groups and verification of severe ischemia.

We introduce a new magnetic resonance (MR) method based on a pixel-by-pixel image processing to examine relationships between metabolic and structural processes in the pathologic hippocampus. The method was tested for lateralization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). Twenty patients with drug-resistant TLE and fifteen healthy controls were examined at 3T. The measurement protocol contained T2-weighted MR images, spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Correlations between quantitative MR parameters were calculated on a pixel-by-pixel basis using the CORIMA program which enables automated pixel identification in the normal tissue according to control data. All MR parameters changed in the anteroposterior direction in the hippocampus and correlation patterns and their slopes differed between patients and controls. Combinations of T2 relaxation times with metabolite values represent the best biomarkers of the epileptogenic zone. Correlations with mean diffusivity did not provide sufficiently accurate results due to diffusion image distortions. Quantitative MR analysis non-invasively provides a detailed description of hippocampal pathology and may represent complementary tool to the standard clinical protocol. However, the automated processing should be carefully monitored in order to avoid possible errors caused by MR artifacts.

Purpose: Dynamic phosphorus magnetic resonance spectroscopy (31P MRS) during and after acute exercise enables the noninvasive in vivo determination of the mitochondrial capacity of skeletal muscle. Nevertheless, the lack of standardization in experimental setups leads to significant variations in published values of maximal aerobic capacity, even in the population of healthy volunteers. Thus, in this study, we aimed to assess the impact of the ergometer type (pneumatic and mechanical resistance construction), radiofrequency (RF)-coil diameter, and different magnetic field strengths (3 and 7 T) on the metabolic parameters measured by dynamic 31P MRS during a plantar flexion isotonic exercise protocol within the same group of healthy volunteers. Methods: Dynamic 31P MRS measurements of the calf muscle in 11 volunteers (mean age, 36 ± 13 yrs; mean BMI, 23.5 ± 2.5 kg/m2), on a 3 T MR system with a custom-made mechanical ergometer in the first research laboratory (RL1) and on 3 and 7 T MR systems equipped with a commercial pneumatic ergometer in the second research laboratory (RL2), were performed at three different workloads. RF-coils differed slightly between the sites and MR systems used. The repeatability of the experimental protocol was tested in every setup. The basal concentrations of phosphocreatine (PCr), exercise-induced depletion of PCr (ΔPCr), initial PCr resynthesis rate (V PCr), and mitochondrial capacity (Q max) were calculated and compared between the research sites and field strengths. Results: High repeatability of the measurement protocol was found in every experimental setup. No significant differences at any workload were found in these metabolic parameters assessed at different magnetic field strengths (3 T vs 7 T), using the same ergometer (in RL2) and a similar RF-coil. In the inter-research laboratory comparison at the same field strength (3 T), but with using different ergometers and RF-coils, differences were found in the concentration of PCr measured at rest and in the drop in PCr signal intensity. These differences translated into difference in the value of mitochondrial capacity at a workload of 15% of maximal voluntary contraction (MVC) force (0.45 ± 0.16 mM/s vs 0.31 ± 0.08 mM/s, in the RL1 and RL2, respectively). Conclusions: Metabolic parameters measured during exercise challenge by dynamic 31P MRS do not depend upon the magnetic field strength used. For multicenter studies with different ergometers, it is important to set the same workload, measurement, and evaluation protocols, especially when the effects of very mild exercise (15% MVC) are to be compared. However, a higher workload (24% MVC) decreases the influence of imperfections and intersite differences for the assessed value of maximal mitochondrial capacity.

The accumulation of iron in the brain is a common physiological process. However, alterations in the deposition of iron or other paramagnetic substances are associated with various diseases. In the present study, the deposition of paramagnetic substances in patients with brain tumours was evaluated using T2 relaxometry. A total of 23 patients with untreated tumours or with recurrent tumours following treatment, together with a group of 19 age-matched healthy controls, were examined using T2 relaxometry at 3T. The relaxation times in the basal ganglia, thalamus and white matter were evaluated. Significantly lower T2 relaxation times were identified in the basal ganglia and thalamus of the patients with tumours, as compared with those of the controls (P

In this study, we present a method for the detection of n-3 fatty acid (n-3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA-PRESS) is based on the selective detection of the CH3 signal of n-3 FA using the MEGA-PRESS (MEshcher–GArwood Point-RESolved Spectroscopy) J-difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co-editing and incomplete subtraction of the CH3 signal of other FAs, which normally obscure the n-3 FA CH3 signal in MR spectra acquired using standard PRESS techniques. The post-processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n-3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n-3 FA estimated by the oMEGA-PRESS method in phantoms showed a highly significant linear correlation with the n-3 FA content determined by gas chromatography. The signal attributed to n-3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n-3 FA signal using oMEGA-PRESS. The presented method may be useful for the non-invasive quantification of n-3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n-3 FA metabolism. Copyright © 2014 John Wiley & Sons, Ltd.

To determine whether acutely-induced supraphysiological hyperinsulinemia influences brain metabolism in patients with type 1 diabetes (D) and healthy controls (C) as detected by MR Spectroscopy. Group D consisted of 4 patients with the average duration of diabetes for 7 years. They were matched according to age, sex and BMI to 4 healthy controls. 1H MR Spectroscopy was performed with a 1.5 Tesla. Spectra were obtained from parietooccipital white matter repeatedly during a 3-h hyperinsulinemic euglycemic clamp with 2 mU.kgˉ¹.minˉ¹. In group D, significantly lower basal concentrations of N-acetylaspartate (p=0.02), choline (p=0.03), creatine (p=0.002) and inositol (p=0.007) were detected compared to C. After the induction of hyperinsulinemia, concentrations of choline, creatine, GABA, inositol, lactate, NAA and composite signal glutamate + glutamine (Glx) stayed stable. The detection of glucose signal is less realiable at 1.5 Tesla but we registered the alteration in glucose concentration (p=0.003) in the whole group. Originally sightly elevated glucose concentration in D decreased on the contrary to the increase of originally lower glucose level in C. In conclusions, brain metabolism was altered in D. Short term supraphysiological euglycemic hyperinsulinemia induced changes in the concentration of brain glucose in both C and D.

Object: In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Materials and methods: A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6months after PI transplantation. Results: It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients. Conclusion: The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification.

Purpose Phosphorus (31P) MR spectroscopic imaging (MRSI) is primarily applied with sensitive, surface radiofrequency (RF) coils that provide inhomogeneous excitation RF field (B1+) and rough localization due to their B1+ and sensitivity (B1−) profiles. A careful and time-consuming pulse adjustment and an accurate knowledge of flip angle (FA) are mandatory for quantification corrections. Materials and Methods In this study, a simple, fast, and universal 31P B1+ mapping method is proposed, which requires fast steady-state MRSI (typically one sixth of normal measurement time) in addition to the typical MRSI acquired within the examination protocol. The FA maps are calculated from the ratio of the signal intensities acquired by these two measurements and were used to correct for the influence of B1+ on the metabolite maps. Results In vitro tests were performed on two scanners (3 and 7 Tesla) using a surface and a volume coil. The calculated FA maps were in good agreement with adjusted nominal FAs and the theoretical calculation using the Biot-Savart law. The method was successfully tested in vivo in the calf muscle and the brain of healthy volunteers (n = 4). The corrected metabolite maps show higher homogeneity compared with their noncorrected versions. Conclusion The calculated FA maps helped with B1+ inhomogeneity corrections of acquired in vivo data, and should also be useful with optimization and testing of pulse performances, or with the construction quality tests of new dual-channel 1H/31P coils. J. Magn. Reson. Imaging 2014;40:391–397. © 2013 Wiley Periodicals, Inc.

Magnetic resonance spectroscopic imaging (MRSI) involves a huge number of spectra to be processed and analyzed. Several tools enabling MRSI data processing have been developed and widely used. However, the processing programs primarily focus on sophisticated spectra processing and offer limited support for the analysis of the calculated spectroscopic maps. In this paper the jSIPRO (java Spectroscopic Imaging PROcessing) program is presented, which is a java-based graphical interface enabling post-processing, viewing, analysis and result reporting of MRSI data. Interactive graphical processing as well as protocol controlled batch processing are available in jSIPRO. jSIPRO does not contain a built-in fitting program. Instead, it makes use of fitting programs from third parties and manages the data flows. Currently, automatic spectra processing using LCModel, TARQUIN and jMRUI programs are supported. Concentration and error values, fitted spectra, metabolite images and various parametric maps can be viewed for each calculated dataset. Metabolite images can be exported in the DICOM format either for archiving purposes or for the use in neurosurgery navigation systems.

In humans, aging is accompanied by the deterioration of the hearing function--presbycusis. The major etiology for presbycusis is the loss of hair cells in the inner ear; less well known are changes in the central auditory system. Therefore, we used 1H magnetic resonance spectroscopy at 3T tomograph to examine metabolite levels in the auditory cortex of three groups of subjects: young healthy subjects less than 30 years old and subjects older than 65 years either with mild presbycusis corresponding to their age or with expressed presbycusis. Hearing function in all subjects was examined by pure tone audiometry (125-16,000 Hz). Significant differences were found in the concentrations of glutamate and N-acetylaspartate, with lower levels in aged subjects. Lactate was particularly increased in subjects with expressed presbycusis. Significant differences were not found in other metabolites, including GABA, between young and elderly subjects. The results demonstrate that the age-related changes of the inner ear are accompanied by a decrease in the excitatory neurotransmitter glutamate as well as a lactate increase in the auditory cortex that is more expressed in elderly subjects with large hearing threshold shifts.

Three magnetic resonance (MR)/fluorescence imaging probes were tested for visualization, cellular distribution, and survival of labeled pancreatic islets in vitro and following transplantation. As T(1) contrast agents (CAs), gadolinium(III) complexes linked to β-cyclodextrin (Gd-F-βCD) or bound to titanium dioxide (TiO2 @RhdGd) were tested. As a T(2) CA, perovskite manganite nanoparticles (LSMO@siF@si) were examined. Fluorescein or rhodamine was incorporated as a fluorescent marker in all probes. Islets labeled with gadolinium(III) CAs were visible as hyperintense spots on MR in vitro, but detection in vivo was inconclusive. Islets labeled with LSMO@siF@si CA were clearly visible as hypointense spots or areas on MR scans in vitro as well as in vivo. All CAs were detected inside the islet cells by fluorescence. Although the vitality and function of the labeled islets was not impaired by any of the tested CAs, results indicate that LSMO@siF@si CA is a superior marker for islet labeling, as it provides better contrast enhancement within a shorter scan time.

Purpose An artificial site for cell or pancreatic islet transplantation can be created using a polymeric scaffold, even though it suffers subcutaneously from improper vascularisation. A sufficient blood supply is crucial for graft survival and function and can be enhanced by transplantation of mesenchymal stem cells (MSCs). The purpose of this study was to assess the effect of syngeneic MSCs on neoangiogenesis and cell engraftment in an artificial site by multimodal imaging. Procedures MSCs expressing a gene for luciferase were injected into the artificial subcutaneous site 7 days after scaffold implantation. MRI experiments (anatomical and dynamic contrast-enhanced images) were performed on a 4.7-T scanner using gradient echo sequences. Bioluminescent images were acquired on an IVIS Lumina optical imager. Longitudinal examination was performed for 2 months, and one animal was monitored for 16 months. Results We confirmed the long-term presence (lasting more than 16 months) of viable donor cells inside the scaffolds using bioluminescence imaging with an optical signal peak appearing on day 3 after MSC implantation. When compared to controls, the tissue perfusion and vessel permeability in the scaffolds were significantly improved at the site with MSCs with a maximal peak on day 9 after MSC transplantation. Conclusions Our data suggest that the maximal signal obtained by bioluminescence and magnetic resonance imaging from an artificially created site between 3 and 9 days after MSC transplantation can predict the optimal time range for subsequent cellular or tissue transplantation, including pancreatic islets.

We discussed the cross section studies and the meta-analysis of published data in children and adolescents with ADHD (both drug naive and receiving stimulant medications), in comparison with healthy children and adolescents of the same age. In children and adolescents with ADHD the deceleration of the maturation dynamics of discrete CNS structures is found, volume reduction and decreased grey matter in prefrontal and occipital regions, which is accompanied by reverse asymmetry of the basal ganglia volume (putamen, nucleus caudate). The above mentioned developmental characteristics are valid only for the ADHD children, who have not been treated by stimulant medications. The stimulant treatment eliminates the mentioned changes into various extend. These developmental changes of CNS structures volume are missing in girls.

Introduction: Monitoring of Pancreatic Islets (PIs) after their transplantation could provide important data related to diabetes treatment; however their visualization is conditioned by the contrast agent use. The aim of this study was to label and visualize PIs labeled by the contrast agents based on Chemical Exchange Saturation Transfer (CEST) owing an advantage of contrast switching on/off and simultaneous visualization of differently treated cell population in one MR experiment. 1.2 Material and methods: Two paramagnetic chelates with europium Eu-DO3A-ae and ytterbium Yb-DO3A-ae were tested for labeling of PIs by pinocytosis and microporation. The toxicity, labeling efficacy and detection threshold were assessed for each agent. In vitro MR imaging of the labeled islets was performed on a 4.7 T scanner using a modified turbo spin-echo (RARE) sequence. 1.3 Results: The sufficient labeling efficacy was observed only by using high agent concentration compromising islet viability. The microporation procedure was not effective for islet labeling because of its invasive nature. The islets labeled by pinocytosis were visualized in a phantom by CEST imaging, however, after a long acquisition time at 4.7 T. 1.4 Conclusion: The low sensitivity of detection and impaired cellular viability of the pancreatic islets labeled by the novel CEST contrast agents represent a challenge for the further implementation of these probes as exogenous cellular labels.