Biomedical subjects

Henrik B W Larsson

Publications and source records attributed to Henrik B W Larsson.

16 recordsLinked to original sources

PubMed2026

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2006

An apparent unidirectional influx constant for manganese as a measure of myocardial calcium channel activity.

PURPOSE: To develop an in vivo MR method for evaluation of myocardial calcium channel activity through quantification of apparent unidirectional manganese influx constants following manganese dipyridoxyl-diphosphate (MnDPDP) infusions. MATERIALS AND METHODS: A total of 10 healthy volunteers were divided in two groups, and received 5 micromol of MnDPDP per kg of body weight intravenously in a 1.5 Tesla scanner over five or 30 minutes, respectively. A fast inversion recovery gradient echo sequence was used to estimate pre- and postcontrast R1 values and to measure signal changes following infusions. By assuming equal longitudinal relaxivity (r1) of the contrast in all tissue compartments, signal changes in blood and myocardial tissue yielded temporal input and tissue contrast concentrations respectively. Through a two-tissue compartment model, apparent unidirectional influx constants (Ki) for myocardial manganese accumulation were estimated. RESULTS: Consistent values for Ki in left ventricular wall were found, with a mean value of 5.96 mL/100 g/minute (SD=0.49; N=10). No statistical significant differences in Ki were found between the two infusion groups. CONCLUSION: Since unidirectional manganese accumulation depends upon intact myocyte membranes with functioning calcium channels, the use of unidirectional manganese influx rates may be a valuable research tool for in vivo studies of myocyte functioning in myocardial disease.

Adult↗

PubMed2006

In vivo quantification of regional myocardial blood flow: validity of the fast-exchange approximation for intravascular T1 contrast agent and long inversion time.

In the present study we investigated the effects of water exchange between intra- and extravascular compartments on absolute quantification of regional myocardial blood flow (rMBF) using a saturation-recovery sequence with a rather long inversion time (TI, 176 ms) and a T1-shortening intravascular contrast agent (CMD-A2-Gd-DOTA). Data were acquired in normal and ischemically injured pigs, with radiolabeled microsphere flow measurements used as the gold standard. Five water exchange rates (fast, 6 Hz, 3 Hz, 1 Hz, and no exchange) were tested. The results demonstrate that the fast-exchange approximation may be appropriate for rMBF quantification using the described experimental setting. Relaxation rate change (DeltaR1) analysis improved the accuracy of the analysis of rMBF compared to the MR signal. In conclusion, the current protocol could provide sufficient accuracy for estimating rMBF assuming fast exchange and a linear relationship between signal and tissue concentration when quantification of precontrast T1 is not an option.

Animals↗

PubMed2005

Increased intracranial volume in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that can be difficult to diagnose and distinguish from each other. STUDY AIMS AND METHODS: Patients with PD and MSA and controls were studied with magnetic resonance imaging (MRI) using tissue segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. RESULTS: Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA patients had significantly smaller substantia nigra and caudate volumes than controls but normal intracranial volume. In both patient groups there was a further trend towards smaller amygdala volumes. DISCUSSION: Increased ICV in PD patients is a new finding that may be explained by genetic factors or compensatory responses to early CNS damage. Atrophy of the amygdala in MSA patients has not been demonstrated with MR before. It might explain why these patients can have hyposmia. The putaminal atrophy found in the PD group may be a trait of the later stages of PD. Segmentation of the substantia nigra can be a useful aid in the diagnosis of PD and MSA.

Aged↗

PubMed2005

Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states.

Acute normobaric hypoxia as well as longstanding hypobaric hypoxia induce pronounced physiological changes and may eventually lead to impairment of cerebral function. The aim of the present study is to investigate the effect of hypoxia on the cerebral activation response as well as to explore possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23% lower in altitude than sea-level adaptation in the normoxic condition, but in the hypoxic condition, no significant differences were found. A small but statistically significant decrease in the apparent diffusion coefficient (ADC) was seen in some brain regions during acute hypoxia, whereas ADC was slightly elevated in high altitude as compared to sea-level adaptation. It is concluded that hypoxia significantly diminishes the BOLD response, and the mechanisms underlying this finding are discussed. Furthermore, altitude adaptation may influence both the magnitude of the activation-related response, as well as micro-structural features.

Acclimatization↗

PubMed2005

The relationship between cerebral blood flow and volume in humans.

The purpose of this study was to establish the relationship between regional CBF and CBV at normal, resting cerebral metabolic rates. Eleven healthy volunteers were investigated with PET during baseline conditions, and during hyper- and hypocapnia. Values for rCBF and rCBV were obtained using 15O-labelled water and carbon monoxide, respectively. The mean value of rCBF using PET was 62 +/- 18 ml 100 g(-1) min(-1) during baseline conditions, with an average increase of 46% during hypercapnia, and a decrease of 29% during hypocapnia; baseline rCBV was 7.7 ml/100 g, with 27% increase during hypercapnia and no significant decrease during hypocapnia. A regionally uniform exponential relationship was confirmed between PaCO2 and rCBF as well as rCBV. It is shown that the theoretical implication of this is that the rCBV vs. rCBF relationship should be modelled by a power function; however, due to pronounced intersubject variability, the goodness of fit for linear and nonlinear models were not significantly different. The results of the study are applied to a numerical estimation of regional brain deoxy-haemoglobin content. Independently of the choice of model for the rCBV vs. rCBF relationship, a nonlinear deoxy-haemoglobin vs. rCBF relationship was predicted, and the implications for the BOLD response are discussed.

Adult↗

PubMed2005

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.

Adult↗

PubMed2004

Evaluation of heart perfusion in patients with acute myocardial infarction using dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: To investigate the diagnostic ability of quantitative magnetic resonance imaging (MRI) heart perfusion in acute heart patients, a fast, multislice dynamic contrast-enhanced MRI sequence was applied to patients with acute myocardial infarction. MATERIALS AND METHODS: Seven patients with acute transmural myocardial infarction were studied using a Turbo-fast low angle shot (FLASH) MRI sequence to monitor the first pass of an extravascular contrast agent (CA), gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Quantitation of perfusion, expressed as Ki (mL/100 g/minute), in five slices, each having 60 sectors, provided an estimation of the severity and extent of the perfusion deficiency. Reperfusion was assessed both by noninvasive criteria and by coronary angiography (CAG). RESULTS: The Ki maps clearly delineated the infarction in all patients. Thrombolytic treatment was clearly beneficial in one case, but had no effect in the two other cases. Over the time-course of the study, normal perfusion values were not reestablished following thrombolytic treatment in all cases investigated. CONCLUSION: This study shows that quantitative MRI perfusion values can be obtained from acutely ill patients following acute myocardial infarction. The technique provides information on both the volume and severity of affected myocardial tissue, enabling the power of treatment regimes to be assessed objectively, and this approach should aid individual patient stratification and prognosis.

Contrast Media↗

PubMed2004

Relaxation enhancing properties of MnDPDP in human myocardium.

PURPOSE: To assess magnitude and duration of changes in myocardial longitudinal relaxation rate (R1) in humans following infusion of the manganese (Mn) releasing contrast agent MnDPDP (Mn-dipyridoxyl-diphosphate). MATERIALS AND METHODS: Fifteen healthy volunteers were divided into three groups. After initial myocardial and liver R1 measurements using an inversion recovery (IR) turbo fast low-angle shot (FLASH) sequence at 1.5 Tesla, the groups were given different doses of intravenous MnDPDP: 5, 10 and 15 micromol/kg body weight, respectively, over 30 minutes. R1 measurements were then repeated at 1, 2, 4, 8, and 24 hours after the infusion ended. RESULTS: The left ventricular wall R1 prevalue was 0.98 second(-1) (+/-0.04). R1 increased on average (all 15 subjects) 0.41 second(-1) (+/-0.09). The increase was present one hour after the end of the infusion, remained relatively constant the next two hours, and then declined gradually. After 24 hours, there was still a moderate R1 elevation present, with an average R1-value of 1.16 (+/-0.05). There were only small differences in myocardial R1 responses between the three doses investigated, which was contrasted by a marked dose-response in liver tissue. CONCLUSION: MnDPDP gave a significant and prolonged rise in myocardial R1 even at a dose of 5 micromol/kg. The R1-values in the myocardium did not increase linearly with higher doses.

Adult↗

PubMed2003

Automatic segmentation of thalamic nuclei from diffusion tensor magnetic resonance imaging.

The nuclei of the thalamus have traditionally been delineated by their distinct cyto/myeloarchitectural appearance on histology. Here, we show that diffusion tensor magnetic resonance imaging (DTI) can noninvasively resolve the major thalamic nuclei based on the characteristic fiber orientation of the corticothalamic/thalamocortical striations within each nucleus. Using an automatic clustering algorithm, we extracted the Talairach coordinates for the individual thalamic nuclei. The center-of-mass coordinates for the segmented nuclei were found to agree strongly with those obtained from a histological atlas. The ability to resolve thalamic nuclei with DTI will allow for morphometric analysis of specific nuclei and improved anatomical localization of functional activation in the thalamus.

Algorithms↗

PubMed2002

[Magnetic resonance and multiple sclerosis I. Conventional diagnostic techniques].

Conventional magnetic resonance imaging (MRI) is still the standard technique in the diagnosis and follow-up of patients with multiple sclerosis (MS), despite low pathological specificity and poor correlation to the disability. The results of T2- and T1-weighted imaging with and without contrast and the lesion characteristics are presented in this review. The numerous differential diagnoses and the diagnostic MRI criteria are also reviewed.

Brain↗

PubMed2002

[Magnetic resonance and multiple sclerosis II. New diagnostic techniques].

Conventional magnetic resonance imaging (MRI) techniques have proved important in the diagnosis and in the follow-up in clinical trials of patients with multiple sclerosis (MS). However, these techniques have low specificity for the pathological changes in the MS lesions, and the correlation between conventional MRI and the disability is poor. The last ten years have seen the development of new techniques with improved sensitivity and increased pathological specificity, such as magnetisation transfer imaging (MTI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging, and functional magnetic resonance imaging (fMRI). These techniques and their contribution to the knowledge about the pathophysiology of MS are described in this review.

Brain↗

PubMed2002

Neurohumoral prediction of left-ventricular morphologic response to beta-blockade with metoprolol in chronic left-ventricular systolic heart failure.

BACKGROUND: In order to tailor therapy in heart failure, a solution might be to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy. AIMS: To evaluate neurohumoral factors as markers for left-ventricular (LV) antiremodelling from metoprolol treatment in patients with chronic LV systolic heart failure. METHODS: Forty-one subjects randomised to placebo or metoprolol were studied with magnetic resonance imaging and blood samples to measure LV dimensions and ejection fraction, epinephrine, norepinephrine, plasma renin activity, aldosterone, atrial (ANP) and brain natriuretic peptides, arginine-vasopressin and endothelin-1 at baseline, 5 weeks and 6 months after randomisation. RESULTS: Baseline ANP was identified as sole independent marker for changes in LV end-diastolic (deltaLVEDVI: r=-0.70, P=0.002), and end-systolic (deltaLVESVI: r=-0.53, P=0.03) volumes during metoprolol treatment. Change in ANP during the study was an independent marker for deltaLVEDVI: r=0.66, P=0.004, and deltaLVESVI: r=0.69, P=0.002 in the entire metoprolol group, but at the individual patient level, results were less clear. CONCLUSION: The pre-treatment plasma level of ANP may be a predictor of LV antiremodelling from treatment with metoprolol in patients with chronic heart failure. However, the potential for individual neurohumoral monitoring of the effects on LV dimensions during beta-blockade appears limited.

Adrenergic beta-Antagonists↗

PubMed2002

Left ventricular remodeling in the first year after acute myocardial infarction and the predictive value of N-terminal pro brain natriuretic peptide.

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) has received much attention because of its severe impact on morbidity and mortality rates. However, the incidence and extent of LV remodeling in a modern infarct population who were offered antiremodeling treatment in compliance with daily clinical practice is unknown. The purpose of this study was to clarify this issue and to evaluate the predictive value of N-terminal pro brain natriuretic peptide (NT-proBNP). METHODS: Forty-two patients with a first transmural MI were examined after 1 week, 1 month, 3 months, 6 months, and 1 year with blood samples and magnetic resonance imaging. RESULTS: In 12 patients (29%), LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) increased by 24% and 22% (P <.0001; P =.01). In 12 patients (29%), LVEDVI and LVESVI decreased by 19% and 23% (P <.0001; P =.0005), whereas the remaining 18 patients (43%) had stable conditions regarding these LV measures. LV ejection fraction at baseline was significantly reduced in all patient categories but was unchanged over time. Elevated NT-proBNP level at baseline was identified as an independent predictor of increase in LVEDVI during follow-up examination (P =.007). A baseline level of NT-proBNP >115 pmol/L identified patients who later had LV dilatation develop with a sensitivity and specificity of 89% and 68% (area under curve = 0.77). CONCLUSION: In this 1-year follow-up study of patients with a first transmural MI, approximately 30% had significant increments develop in LVEDVI and LVESVI, and LV ejection fraction remained unchanged. Patients in whom LV dilatation developed could be identified early after the MI with elevated plasma levels of NT-proBNP.

Biomarkers↗

PubMed2002

Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations.

BACKGROUND: Brain- and N-terminal pro brain natriuretic peptide (NT-proBNP) have been identified as promising markers for heart failure. However, previous studies have revealed that they may hold insufficient diagnostic power for implementation into clinical practice because of a significant overlap in the range of plasma levels between healthy subjects and subjects with heart failure. We hypothesized that imprecision of the reference method (ie, the echocardiographic evaluation of left ventricular [LV] function) may have affected results from those earlier studies. We therefore wanted to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements. METHODS: Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples and magnetic resonance imaging along with 20 age-matched and gender-matched healthy control subjects. RESULTS: NT-proBNP was associated with LV end-diastolic (r = 0.69; P <.0001) and end-systolic (r = 0.73; P <.0001) volume indices, LV mass index (r = 0.69; P <.0001), and LV ejection fraction (r = -0.75; P <.0001). Receiver operating characteristic curves were calculated for the ability of NT-proBNP to detect LV end-diastolic volume index (>105 mL. m(-2)[cut-off]; sensitivity/specificity, 82%/87%), LV end-systolic volume index (>35 mL. m(-2); sensitivity/specificity, 86%/86%), LV mass index (>152 g. m(-2); sensitivity/specificity, 85%/86%), and LV ejection fraction (<58%; sensitivity/specificity, 84%/85%) deviating more than 2 standard deviations from control values. CONCLUSION: NT-proBNP is a powerful marker for LV dimensions and systolic function in patients with heart failure and discriminates well between healthy subjects and subjects with impaired LV systolic function or increased LV dimensions.

Aged↗

PubMed2002

Decreased myocardial perfusion reserve in diabetic autonomic neuropathy.

The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN-) and 10 healthy control subjects. Baseline myocardial perfusion index (K(i)) was similar in the three groups (AN+ 88.6 +/- 8.7 ml. 100 g(-1). min(-1), AN- 82.6 +/- 7.2, control subjects 93.7 +/- 9.0) (means +/- SE). K(i) during Dipyridamole vasodilatation was significantly lower in the patients with autonomic neuropathy (P < 0.001) than in the other groups (AN+ 131.1 +/- 13.0 ml. 100 g(-1). min(-1), AN- 177.3 +/- 8.6, control subjects 197.2 +/- 8.9). Mean blood pressure was unchanged during Dipyridamole infusion in AN- and control subjects, whereas a significant blood pressure decrease was found in AN+ (15.6 +/- 2.6 mmHg, P < 0.025). There was a significant correlation between blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate for the increase in mortality in these patients. The underlying mechanism may be defective myocardial sympathetic vasodilatation, a lack of ability to maintain blood pressure during vasodilatation, or both.

Adult↗