In vivo calibration of the T2* cardiovascular magnetic resonance method at 1.5 T for estimation of cardiac iron in a minipig model of transfusional iron overload.

BACKGROUND: Non-invasive estimation of the cardiac iron concentration (CIC) by T2* cardiovascular magnetic resonance (CMR) has been validated repeatedly and is in widespread clinical use. However, calibration data are limited, and mostly from post-mortem studies. In the present study, we performed an in vivo calibration in a dextran-iron loaded minipig model. METHODS: R2* (= 1/T2*) was assessed in vivo by 1.5 T CMR in the cardiac septum. Chemical CIC was assessed by inductively coupled plasma-optical emission spectroscopy in endomyocardial catheter biopsies (EMBs) from cardiac septum taken during follow up of 11 minipigs on dextran-iron loading, and also in full-wall biopsies from cardiac septum, taken post-mortem in another 16  minipigs, after completed iron loading. RESULTS: A strong correlation could be demonstrated between chemical CIC in 55 EMBs and parallel cardiac T2* (Spearman rank correlation coefficient 0.72, P < 0.001). Regression analysis led to [CIC] = (R2* - 17.16)/41.12 for the calibration equation with CIC in mg/g dry weight and R2* in Hz. An even stronger correlation was found, when chemical CIC was measured by full-wall biopsies from cardiac septum, taken immediately after euthanasia, in connection with the last CMR session after finished iron loading (Spearman rank correlation coefficient 0.95 (P < 0.001). Regression analysis led to the calibration equation [CIC] = (R2* - 17.2)/31.8. CONCLUSIONS: Calibration of cardiac T2* by EMBs is possible in the minipig model but is less accurate than by full-wall biopsies. Likely explanations are sampling error, variable content of non-iron containing tissue and smaller biopsies, when using catheter biopsies. The results further validate the CMR T2* technique for estimation of cardiac iron in conditions with iron overload and add to the limited calibration data published earlier.

Consequences of parenteral iron-dextran loading investigated in minipigs. A new model of transfusional iron overload.

Patients with blood transfusion-dependent anemias develop transfusional iron overload (TIO), which may cause cardiosiderosis. In patients with an ineffective erythropoiesis, such as thalassemia major, common transfusion regimes aim at suppression of erythropoiesis and of enteral iron loading. Recent data suggest that maintaining residual, ineffective erythropoiesis may protect from cardiosiderosis. We investigated the common consequences of TIO, including cardiosiderosis, in a minipig model of iron overload with normal erythropoiesis. TIO was mimicked by long-term, weekly iron-dextran injections. Iron-dextran loading for around one year induced very high liver iron concentrations, but extrahepatic iron loading, and iron-induced toxicities were mild and did not include fibrosis. Iron deposits were primarily in reticuloendothelial cells, and parenchymal cardiac iron loading was mild. Compared to non-thalassemic patients with TIO, comparable cardiosiderosis in minipigs required about 4-fold greater body iron loads. It is suggested that this resistance against extrahepatic iron loading and toxicity in minipigs may at least in part be explained by a protective effect of the normal erythropoiesis, and additionally by a larger total iron storage capacity of RES than in patients with TIO. Parenteral iron-dextran loading of minipigs is a promising and feasible large-animal model of iron overload, that may mimic TIO in non-thalassemic patients.

Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy Study.

BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective serotonin and norepinephrine reuptake inhibitor, and to explore the association between metabolite changes and the analgesic effect and side effects. METHODS: Single voxel proton spectroscopy measurements were performed in the anterior cingulate cortex, insula and prefrontal cortex in 20 healthy subjects before and after treatment for 5 days with oxycodone (eight doses of 10 mg extended release), venlafaxine (eight doses of 37.5 mg extended release) or placebo in a randomized double-blind fashion. The metabolites of glutamate, N-acetylaspartate, and myo-inositol were analyzed in ratios to creatine. RESULTS: Including all areas, the glutamate/creatine ratio was decreased (P < .05) with 8.4% ± 0.3% after oxycodone treatment (P = .02) and 6.6% ± 0.4% after venlafaxine treatment (P = .07) as compared to placebo. No statistical significant differences in treatment effects across the areas were found (P = .6). No treatment effect was seen for N-acetylaspartate/creatine or myo-inositol/creatine ratios (all P > .05). No associations between treatment induced glutamate/creatine changes and the analgesic effect and side effects were demonstrated (all P > .05). CONCLUSIONS: MRS can be used to detect brain metabolites following acute analgesic treatments and glutamate is central in these mechanisms. Consequently, MRS might be a valuable tool to objectively evaluate analgesic effects and a potential biomarker to predict treatment outcomes and more research is needed.

Cingulate metabolites during pain and morphine treatment as assessed by magnetic resonance spectroscopy.

BACKGROUND: Experimental investigation of cerebral mechanisms underlying pain and analgesia are important in the development of methods for diagnosis and treatment of pain. The aim of the current study was to explore brain metabolites in response to pain and treatment with morphine. METHODS: Proton magnetic resonance spectroscopy of the anterior cingulate cortex was performed in 20 healthy volunteers (13 males and seven females, aged 24.9±2.6 years) during rest and acute pain before and during treatment with 30 mg of oral morphine or placebo in a randomized, double-blinded, cross-over study design. Pain was evoked by skin stimulation applied to the right upper leg using a contact heat-evoked potential stimulator. RESULTS: Data from 12 subjects were valid for analysis. Painful stimulation induced an increase in N-acetylaspartate/creatine compared with rest (F=5.5, P=0.04). During treatment with morphine, painful stimulation induced decreased glutamate/creatine (F=7.3, P=0.02), myo-inositol/creatine (F=8.38, P=0.02), and N-acetylaspartate/creatine (F=13.8, P=0.004) concentrations, whereas an increase in the pain-evoked N-acetylaspartate/creatine concentration (F=6.1, P=0.04) was seen during treatment with placebo. CONCLUSION: This explorative study indicates that neuronal metabolites in the anterior cingulate cortex, such as N-acetylaspartate, glutamate, and myo-inositol, could be related to the physiology of pain and treatment with morphine. This experimental method has the potential to enable the study of brain metabolites involved in pain and its treatment, and may in the future be used to provide further insight into these mechanisms.

Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging.

INTRODUCTION: The purpose of this study was to compare the non-invasive 3D pseudo-continuous arterial spin labelling (PC ASL) technique with the clinically established dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI) for evaluation of brain tumours. METHODS: A prospective study of 28 patients with contrast-enhancing brain tumours was performed at 3 T using DSC-MRI and PC ASL with whole-brain coverage. The visual qualitative evaluation of signal enhancement in tumour was scored from 0 to 3 (0 = no signal enhancement compared with white matter, 3 = pronounced signal enhancement with equal or higher signal intensity than in grey matter/basal ganglia). The extent of susceptibility artefacts in the tumour was scored from 0 to 2 (0 = no susceptibility artefacts and 2 = extensive susceptibility artefacts (maximum diameter > 2 cm)). A quantitative analysis was performed with normalised tumour blood flow values (ASL nTBF, DSC nTBF): mean value for region of interest (ROI) in an area with maximum signal enhancement/the mean value for ROIs in cerebellum. RESULTS: There was no difference in total visual score for signal enhancement between PC ASL and DSC relative cerebral blood flow (p = 0.12). ASL had a lower susceptibility-artefact score than DSC-MRI (p = 0.03). There was good correlation between DSC nTBF and ASL nTBF values with a correlation coefficient of 0.82. CONCLUSION: PC ASL is an alternative to DSC-MRI for the evaluation of perfusion in brain tumours. The method has fewer susceptibility artefacts than DSC-MRI and can be used in patients with renal failure because no contrast injection is needed.