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.
Objective Magnetic resonance imaging (MRI)-based techniques for non-invasive assessing liver iron concentration (LIC) in patients with iron overload have a limited upper measuring range around 35 mg/g dry weight, caused by signal loss from accelerated T1-, T2-, T2* shortening with increasing LIC. Expansion of this range is necessary to allow evaluation of patients with very high LIC. Aim To assess measuring range of a gradient-echo R2* method and a T1-weighted spin-echo (SE), signal intensity ratio (SIR)-based method (TE = 25 ms, TR = 560 ms), and to extend the upper measuring range of the SIR method by optimizing echo time (TE) and repetition time (TR) in iron-loaded minipigs. Methods Thirteen mini pigs were followed up during dextran-iron loading with repeated percutaneous liver biopsies for chemical LIC measurement and MRIs for parallel non-invasive estimation of LIC (81 examinations) using different TEs and TRs. Results SIR and R2* method had similar upper measuring range around 34 mg/g and similar method agreement. Using TE = 12 ms and TR = 1200 ms extended the upper measuring range to 115 mg/g and yielded good method of agreement. Discussion The wider measuring range is likely caused by lesser sensitivity of the SE sequence to iron, due to shorter TE, leading to later signal loss at high LIC, allowing evaluation of most severe hepatic iron overload. Validation in iron-loaded patients is necessary.
Background/aims Data on mechanical sensitivity and cutaneous allodynia in different types and phases of migraine headaches are limited. Existence and pattern of such symptoms may advance the understanding of neurophysiological mechanisms, assist clinical evaluation of the patients, and further improve management. Hence, in a large controlled study on migraine patients, mechanical sensitivity and cutaneous allodynia were assessed together with clinical markers. Methods Sensitivity to mechanical stimuli was measured in migraine patients during attack (within 2 h of headache onset), within remission phase (48–72 h after headache onset), and in pain-free periods (>5 days pain-free) in comparison with sex-and age-matched healthy controls. Pin-prick stimulation was performed in the temple region in the pain-referred side using weight-calibrated pins (8, 16, 32, 64, 128, 256 mN) in a randomized order (3 stimuli lasting 2 s), with the patient rating the sensation on a 10-point numerical scale. Pressure Pain Threshold (PPT) was assessed using a handheld algometer (1 cm2 rubber probe) over the anterior aspect of the temporal muscle (30 kPa/s, 3 times). Results Preliminary analysis revealed increased mechanical sensitivity to Pin-prick during all phases in migraine patients (n = 4) compared to healthy controls (n = 5), and likewise increased during attack and remission phases compared to pain-free periods within patients. PPT, assessing mainly muscle nociception, showed a tendency to decline during attack and remission phases (89 ± 13% and 82 ± 6%, respectively) compared to pain-free periods, with even higher sensitivity during attack and remission phases (80 ± 12% and 75 ± 11.1%, respectively) compared to healthy controls. Conclusions The current preliminary observed tendencies imply the presence of mechanical hypersensitivity in migraine patients with a notable change during attack and remission phases. This study is ongoing and no firm conclusion can be stated. In addition, alteration of mechanical sensitivity in different phases will be correlated to objective assessments of biological markers in serum specimens of the study population.
Gastroenteropathy is a common complication in diabetes associated with damages to the enteric nervous system. Systemic low-grade inflammation facilitates neurotoxicity, and associations with peripheral and autonomic neuropathy have been reported. However, less is known of associations with gastroenteropathy. To explore the area cross-sectionally, we included individuals with diabetes (type 1: 56, type 2: 100) and 21 healthy controls. Serum levels of interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by multiplex technology. Segmental gastrointestinal transit times were assessed by wireless motility capsule investigations. Symptoms of gastroparesis were rated on Gastroparesis Cardinal Symptom Index questionnaires. Compared to healthy, levels of TNF-α were decreased in type 1 diabetes and increased in type 2 diabetes, while colonic transit time was increased (all p < 0.05). In diabetes, associations between IL-8 and prolonged gastric emptying (odds ratio (OR) 1.07, p = 0.027) and between IL-10 and prolonged colonic transit (OR 29.99, p = 0.013) were seen. Inverse correlations between IL-6 and nausea/vomiting (rho = −0.19, p = 0.026) and bloating (rho = −0.29; p < 0.001) were found. These findings indicate a plausible interaction between inflammation and the enteric nervous system in diabetes, which raises the question of whether anti-inflammatory strategies could be applied in management of diabetic gastroenteropathy.
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