Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients.

OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID. MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies. RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91). DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

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 (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

In Vitro 31P MR Chemical Shifts of In Vivo-Detectable Metabolites at 3T as a Basis Set for a Pilot Evaluation of Skeletal Muscle and Liver 31P Spectra with LCModel Software.

Most in vivo 31P MR studies are realized on 3T MR systems that provide sufficient signal intensity for prominent phosphorus metabolites. The identification of these metabolites in the in vivo spectra is performed by comparing their chemical shifts with the chemical shifts measured in vitro on high-field NMR spectrometers. To approach in vivo conditions at 3T, a set of phantoms with defined metabolite solutions were measured in a 3T whole-body MR system at 7.0 and 7.5 pH, at 37 °C. A free induction decay (FID) sequence with and without 1H decoupling was used. Chemical shifts were obtained of phosphoenolpyruvate (PEP), phosphatidylcholine (PtdC), phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), glycerophosphoetanolamine (GPE), uridine diphosphoglucose (UDPG), glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), 2,3-diphosphoglycerate (2,3-DPG), nicotinamide adenine dinucleotide (NADH and NAD+), phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and inorganic phosphate (Pi). The measured chemical shifts were used to construct a basis set of 31P MR spectra for the evaluation of 31P in vivo spectra of muscle and the liver using LCModel software (linear combination model). Prior knowledge was successfully employed in the analysis of previously acquired in vivo data.

Origin of the 31 P MR signal at 5.3 ppm in patients with critical limb ischemia.

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.

31 P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations.

Skeletal muscle phosphorus-31 31 P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31 P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31 P MRS methods can probe it. Here we consider basic signal-acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with 31 P MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near-infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and 1 H MRS measurements) can help in the physiological/metabolic interpretation of 31 P MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology.

Multiparametric Quantitative Brain MRI in Neurological and Hepatic Forms of Wilson's Disease.

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 < 0.05 was considered significant. RESULTS: Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T2 and T2 * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T2 in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T1 at both field strengths (P < 0.001 to both groups), and an increased T2 at 1.5T only (P < 0.001 to both groups). DATA CONCLUSION: We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.

MR compatible ergometers for dynamic 31P MRS.

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.

The aging effect on prostate metabolite concentrations measured by 1H MR spectroscopy.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the assessment of limb ischemia and effect of revascularization]. / Syndrom diabetické nohy: význam MR spektroskopie lýtkových svalu pro hodnocení koncetinové ischemie a efektu revaskularizace.

AIM: 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. METHODS: 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. RESULTS: Patients with CLI had significantly lower PCr/Pi (p < 0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax and prolonged τPCr (both p < 0.001) 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, p < 0.005). 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. CONCLUSION: 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.

Reverse asymmetry and changes in brain structural volume of the basal ganglia in ADHD, developmental changes and the impact of stimulant medications.

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.

Long term pharmacotherapy by methylfenidate or atomoxetine DAT 1 10/10 ADHD children in correlation with results of the imaging methods.

OBJECTIVES: ADHD is one of the most significant diagnostic units in child and adolescent psychiatry. The occurrence in children is 5-6% and 50-80% continued to adult age. The presence of individual genes (polymorphism) on particular symptoms and processes in ADHD are not known. It is estimated that ADHD symptoms are up to 80% to genetic. The higher density of resultant DAT 1 protein was observed in ADHD patients in comparison with controls. The question was if DAT 1 10/10 predicted bad prognoses in long term therapy. METHODS: We compared 30 ADHD DAT 1 10/10 adolescents treated for 5-6 years. Patients with 30 control adolescents. They were the same age of probands and controls. All these subjects were examined by child psychiatry scales (Conners, Achenbach…). Biological changes were tested by MRI specific CNS volumometry. RESULTS: We didn't confirm bad prognoses in long term therapy with methylphenidate or atomoxetine in ADHD children DAT 1 10/10 in long term therapy. In MRI specific CNS volumometry were not identify any differences in controls and ADHD probands. Gray matter thickness was significantly higher in prefrontal and occipital areas in patients compared to control in prefrontal and occipital areas with cluster-wise p-value<0.05. By this method were not identify any cerebrum damage in long term therapy by methylphenidate and atomoxetine.

Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS: The aim of the study was to compare the effect of six (A6 regimen) vs two meals a day, breakfast and lunch (B2 regimen), on body weight, hepatic fat content (HFC), insulin resistance and beta cell function. METHODS: In a randomised, open, crossover, single-centre study (conducted in Prague, Czech Republic), we assigned 54 patients with type 2 diabetes treated with oral hypoglycaemic agents, both men and women, age 30-70 years, BMI 27-50 kg/m(2) and HbA1c 6-11.8% (42-105 mmol/mol), to follow two regimens of a hypoenergetic diet, A6 and B2, each for 12 weeks. Randomisation and allocation to trial groups (n = 27 and n = 27) were carried out by a central computer system. Individual calculations of energy requirements for both regimens were based on the formula: (resting energy expenditure × 1.5) - 2,092 kJ. The diet in both regimens had the same macronutrient and energy content. HFC was measured by proton magnetic resonance spectroscopy. Insulin sensitivity was measured by isoglycaemic-hyperinsulinaemic clamp and calculated by mathematical modelling as oral glucose insulin sensitivity (OGIS). Beta cell function was assessed during standard meal tests by C-peptide deconvolution and was quantified with a mathematical model. For statistical analysis, 2 × 2 crossover ANOVA was used. RESULTS: The intention-to-treat analysis included all participants (n = 54). Body weight decreased in both regimens (p < 0.001), more for B2 (-2.3 kg; 95% CI -2.7, -2.0 kg for A6 vs -3.7 kg; 95% CI -4.1, -3.4 kg for B2; p < 0.001). HFC decreased in response to both regimens (p < 0.001), more for B2 (-0.03%; 95% CI -0.033%, -0.027% for A6 vs -0.04%; 95% CI -0.041%, -0.035% for B2; p = 0.009). Fasting plasma glucose and C-peptide levels decreased in both regimens (p < 0.001), more for B2 (p = 0.004 and p = 0.04, respectively). Fasting plasma glucagon decreased with the B2 regimen (p < 0.001), whereas it increased (p = 0.04) for the A6 regimen (p < 0.001). OGIS increased in both regimens (p < 0.01), more for B2 (p = 0.01). No adverse events were observed for either regimen. CONCLUSIONS/INTERPRETATION: Eating only breakfast and lunch reduced body weight, HFC, fasting plasma glucose, C-peptide and glucagon, and increased OGIS, more than the same caloric restriction split into six meals. These results suggest that, for type 2 diabetic patients on a hypoenergetic diet, eating larger breakfasts and lunches may be more beneficial than six smaller meals during the day. Trial registration ClinicalTrials.gov number, NCT01277471, completed. Funding Grant NT/11238-4 from Ministry of Health, Prague, Czech Republic and the Agency of Charles University - GAUK No 702312.

Flip-angle mapping of 31P coils by steady-state MR spectroscopic imaging.

PURPOSE: Phosphorus ((31)P) 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 (31)P 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 (1)H/(31)P coils.

Technical note: MR-compatible pedal ergometer with electromechanical pedal resistance and exercise triggering enhanced by visual feedback via video display.

BACKGROUND: During and after exercise, dynamic 31 P MR parameters are typically measured using an MR-compatible ergometer. Self-built equipment for local condition can be constructed where possible. PURPOSE: To develop a pedal resistance ergometer with rocker arm based on a system that combines electric weight displacement, visual self-monitoring, and exercise triggering. The repeatability and reproducibility were tested. METHODS: The hardware and software for the ergometer were constructed from commercial components in a home laboratory. Twelve volunteers participated in the testing of the ergometer. RESULTS: A fully automated ergometer system was developed, allowing the pedal resistance to be adjusted during the examination. The system includes a self-monitoring and triggering mechanism that enables both the operator and subject to monitor pedal frequency and force. The operator can modify the pedal resistance as desired during the exercise. This self-monitoring solution is simple and cost-effective, requiring only a commercial potentiometer, an Arduino converter, and a conventional video projector with a personal computer (PC). Additionally, all system components are located outside the magnetic resonance (MR) room, avoiding interference with the MR system. Results of several test of the reproducibility/repeatability of power at three pedal resistance values (15%, 24%, 25% maximal voluntary force) were expressed both as a coefficient of variation ranging from 6% to 3.1% and as an intraclass correlation of coefficient ranging from 0.96 to 0.99. Similar values were also found for other dynamic parameters of 31 P MR spectroscopy. These findings are similar to published data obtained on different types of ergometers. CONCLUSIONS: Based on more than 1 year of usage, the ergometer proved successful in handling stationary and variable loads, and can be easily operated by a single user.

Changes in the brain during long-term follow-up after liver transplantation.

PURPOSE: To examine changes in the brain before liver transplantation caused by the accumulation of paramagnetic ion deposits and to investigate recovery after liver transplantation over a long-term horizon. MATERIALS AND METHODS: Fifteen patients indicated for liver transplantation, 26 patients up to 2 years after, and 40 patients 8-15 years after liver transplantation were subjected to MR relaxometry. T(1) and T(2) relaxation times in the basal ganglia, thalamus, and white matter were evaluated. RESULTS: Relaxometry revealed a shortening of the relaxation times due to the deposition of paramagnetic ions in the basal ganglia before liver transplantation (P < 0.05), complete normalization of the relaxation times shortly after transplantation in the globus pallidus and caudate nucleus, and partial recovery of T(2) in the putamen. Relaxation times remained stable even 15 years posttransplantation. Increased relaxation times posttransplantation were found in the white matter and thalamus. CONCLUSION: The shortening of the relaxation times observed in the basal ganglia before liver transplantation was caused by paramagnetic ion deposition. The recovery observable within 2 years after transplantation was permanent, and no recurrence of paramagnetic ion deposition was observed even 15 years posttransplantation. Changes in the white matter and thalamus after transplantation were attributed to damage caused by permanent exposure to immunosuppressants.

Quantitative MR imaging and spectroscopy of brain tumours: a step forward?

OBJECTIVES: A prospective quantitative MR study of brain tumours was performed to show the potential of combining different MR techniques to distinguish various disease processes in routine clinical practice. METHODS: Twenty-three patients with various intracranial tumours before treatment (diagnosis confirmed by a biopsy) and 59 healthy subjects were examined on a 3-T system by conventional MR imaging, 1H spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Metabolic concentrations and their ratios, T2 relaxation times and mean diffusivities were calculated and correlated on a pixel-by-pixel basis and compared to control data. RESULTS: Different tumour types and different localisations revealed specific patterns of correlations between metabolic concentrations and mean diffusivity or T2 relaxation times. The patterns distinguish given tissue states in the examined area: healthy tissue, tissue infiltrated by tumour, active tumour, oedema infiltrated by tumour, oedema, etc. This method is able to describe the complexity of a highly heterogeneous tissue in the tumour and its vicinity, and determines crucial parameters for tissue differentiation. CONCLUSIONS: A combination of different MR parameters on a pixel-by-pixel basis in individual patients enables better identification of the tumour type, direction of proliferation and assessment of the tumour extension. KEY POINTS : • Magnetic resonance offers many different methods of examining the brain. • A combination of quantitative MR parameters helps distinguish different brain lesions • Different tumour types revealed specific correlation patterns amongst different MR parameters • The correlation patterns reflect highly heterogeneous complex tissue within tumours.

Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n-3 polyunsaturated fatty acids (n-3-PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n-3-PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double-blind placebo-controlled trial (3.6 g/day n-3-PUFA vs. placebo). During the 1-year follow-up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n-3-PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment-and weight reduction-was observed; furthermore, this effect was clearly potentiated by n-3-PUFA treatment (P < 0.005). In addition, n-3-PUFA treatment resulted in substantial changes in the plasma lipidome, with n-3-PUFA-enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n-3-PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.

MR spectroscopy as a tool for in vivo determination of steatosis in liver transplant recipients.

OBJECT: Among several non-invasive methods of liver fat analysis, the most important role is played by MR imaging and spectroscopy (MRS). This study describes the 1H MRS at 3T measurement of liver fat volume fraction Φ(fat) in a group of liver transplant patients, an at-risk group for the development of de novo steatosis. MATERIALS AND METHODS: Seventy-seven liver transplant recipients who underwent routine protocolar posttransplant examination were divided into three groups: CON-PAT (control group for the cross validation test, 48 patients), PAT-PAT (patients test group for the cross validation test, 29 patients), and PAT (pooled data). Single voxel 1H MRS at 3T was used for the determination of Φ(fat) and histology results (His) were used as the reference standard. RESULTS: Linear and non-linear regression models were used to describe the relationship between Φ(fat) and His. Strong correlation was found for both models with r = 0.83-0.94 (P < 0.001); a higher r was found for non-linear regression in all tested groups. Areas under receiver operation curves were calculated for cut points His ≥ 5 and > 33% and were found in the range of 0.77-0.86. Fibrosis influences the calculation of Φ(fat) and different slopes were obtained for fibrosis stages F0-F1 and F2-F3, respectively. CONCLUSION: Significant correlation was found between the results of histology and 1H MRS measurement of liver fat content. The method is suitable for non-invasive repetitive examination of liver fat in liver-transplants patients between protocol biopsies and for the screening of steatosis in other liver diseases.

[Determination of liver triglycerides by 1H MR spectroscopy]. / Stanovení obsahu jaterního tuku metodou 1H MR spektroskopie.

BACKGROUND: Metabolic syndrome is responsible for increasing the fat content of the liver. Among several non-invasive methods of liver fat analysis, the most important role is played by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). This pilot study describes the methodology for measurements of triglycerides in the liver in a group of liver transplant patients using 1H MRS at 3T. METHODS AND RESULTS: Thirty-eight patients (12 Female, 27 male, aged 19-71) who underwent routine preventive examination at IKEM were included in the MRS study. The fat content of liver biopsies was classified according to the number of affected hepatocytes, HIS. Based on this classification, there were 20 patients with a steatosis score of S0, 15 patients with a score of S1, 2 patients with a score of S2 and 1 patient with a score of S3. 1H MR spectra were measured from three positions in the liver. Following Longo et al, the concentration of fat phi(fat), was calculated from the signal intensities of water and triglycerides. Linear correlation between the number of affected hepatocytes and fat content was described by the equation: HIS = 6.4 phi(fat) -2.1; r2 = 0.85; p = 0.001. CONCLUSIONS: The pilot study confirmed that examination of fat content using 1H MRS at 3T is well tolerated by patients. Significant correlation was found between the results of histology and 1H MRS measurement of liver fat content. The method is suitable for non-invasive repetitive and screening examination measurement of fat in the liver.

Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation.

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.