61 results on '"Anna-Maija Häkkinen"'
Search Results
2. Application of Self-Organising Maps in Automated Chemical Shift Correction of In Vivo H MR Spectra.
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Juhani Pulkkinen, Mika Lappalainen, Anna-Maija Häkkinen, Nina Lundbom, Risto A. Kauppinen, and Yrjö Hiltunen
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- 2002
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3. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance
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Jan Borén, Satu Vehkavaara, Jukka Westerbacka, Chris J. Packard, Sven-Olof Olofsson, Martin Adiels, Aino Soro-Paavonen, Anna-Maija Häkkinen, Marja-Riitta Taskinen, Hannele Yki-Järvinen, and Muriel J. Caslake
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Adult ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,Fatty Acids, Nonesterified ,Lipoproteins, VLDL ,Body Mass Index ,Insulin resistance ,Reference Values ,Internal medicine ,Diabetes mellitus ,Abdomen ,Internal Medicine ,medicine ,Humans ,Insulin ,Pancreatic hormone ,Apolipoproteins B ,biology ,Middle Aged ,medicine.disease ,Kinetics ,Endocrinology ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Liver ,biology.protein ,Insulin Resistance ,Steatosis - Abstract
Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content.A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group.The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased.Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.
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- 2007
4. Adipose Tissue Inflammation and Increased Ceramide Content Characterize Subjects With High Liver Fat Content Independent of Obesity
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Robert Bergholm, Maria Kolak, Vidya Velagapudi, Janne Makkonen, Rachel M. Fisher, Hannele Yki-Järvinen, Dick Wågsäter, Aila Rissanen, Monica Lindell, Per Eriksson, Laxman Yetukuri, Anders Hamsten, Jukka Westerbacka, Anna-Maija Häkkinen, and Matej Orešič
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Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Adipose tissue ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin ,0303 health sciences ,Fatty liver ,Fasting ,Middle Aged ,Immunohistochemistry ,3. Good health ,Adipose Tissue ,Health ,Plasminogen activator inhibitor-1 ,Cytokines ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Adolescent ,Antigens, Differentiation, Myelomonocytic ,030209 endocrinology & metabolism ,Inflammation ,Biology ,Ceramides ,03 medical and health sciences ,Insulin resistance ,SDG 3 - Good Health and Well-being ,Antigens, CD ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Internal Medicine ,medicine ,Humans ,Obesity ,RNA, Messenger ,Triglycerides ,Cell Size ,030304 developmental biology ,Adiponectin ,Cholesterol ,Macrophages ,Cholesterol, HDL ,medicine.disease ,Blood Cell Count ,Fatty Liver ,Endocrinology ,Gene Expression Regulation ,chemistry - Abstract
OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor-γ and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
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- 2007
5. Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes
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Leena Juurinen, Anna-Maija Häkkinen, Mirja Tiikkainen, Hannele Yki-Järvinen, and Antti Hakkarainen
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medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,Fatty Acids, Nonesterified ,Insulin resistance ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Insulin ,Pancreatic hormone ,business.industry ,Alanine Transaminase ,Middle Aged ,medicine.disease ,Lipids ,Metformin ,Drug Combinations ,Glucose ,Endocrinology ,Diabetes Mellitus, Type 2 ,Liver ,Basal metabolic rate ,Basal Metabolism ,Insulin Resistance ,Steatosis ,business ,Oxidation-Reduction ,Body mass index - Abstract
We determined whether insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes (age 51 ± 2 yr, body mass index 33.1 ± 1.4 kg/m2) treated with metformin alone received additional basal insulin for 7 mo. Liver fat (proton magnetic resonance spectroscopy), fat distribution (MRI), fat-free and fat mass, and whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp combined with infusion of [3-3H]glucose) were measured. The insulin dose averaged 75 ± 10 IU/day (0.69 ± 0.08 IU/kg, range 24–132 IU/day). Glycosylated hemoglobin A1c(Hb A1c) decreased from 8.9 ± 0.3 to 7.4 ± 0.2% ( P < 0.001). Whole body insulin sensitivity increased from 2.21 ± 0.38 to 3.08 ± 0.40 mg/kg fat-free mass (FFM)·min ( P < 0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production (HGP) by insulin (HGP 1.04 ± 0.28 vs. 0.21 ± 0.19 mg/kg FFM·min, P < 0.01). The percent suppression of HGP by insulin increased from 72 ± 8 to 105 ± 11% ( P < 0.01). LFAT decreased from 17 ± 3 to 14 ± 3% ( P < 0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity ( r = 0.56, P < 0.05). Body weight increased by 3.0 ± 1.1 kg ( P < 0.05). Of this, 83% was due to an increase in fat-free mass ( P < 0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly. Conclusions: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.
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- 2007
6. Uridine Supplementation for the treatment of Antiretroviral Therapy-Associated Lipoatrophy: A Randomized, Double-Blind, Placebo-Controlled Trial
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Ksenia Sevastianova, Hartwig Klinker, Hannele Yki-Järvinen, Jussi Sutinen, Anna-Maija Häkkinen, Matti Ristola, and Ulrich A. Walker
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Male ,medicine.medical_specialty ,Randomization ,medicine.medical_treatment ,Subcutaneous Fat ,Placebo-controlled study ,Administration, Oral ,HIV Infections ,Gastroenterology ,Drug Administration Schedule ,law.invention ,Absorptiometry, Photon ,Double-Blind Method ,Randomized controlled trial ,law ,Antiretroviral Therapy, Highly Active ,Internal medicine ,medicine ,Body Fat Distribution ,Humans ,Pharmacology (medical) ,Uridine ,Lipoatrophy ,Pharmacology ,Chemotherapy ,business.industry ,HIV-Associated Lipodystrophy Syndrome ,Spectrum Analysis ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Reverse transcriptase ,Mitochondrial toxicity ,Treatment Outcome ,Infectious Diseases ,Endocrinology ,Anti-Retroviral Agents ,Dietary Supplements ,Body Composition ,HIV-1 ,Female ,business ,Nucleoside - Abstract
BackgroundHighly active antiretroviral therapy (HAART) is associated with loss of subcutaneous fat (lipoatrophy) presumably due to mitochondrial toxicity of nucleoside reverse transcriptase inhibitors. In vitro, uridine abrogates thymidine analogue-induced toxicity in adipocytes.MethodsA total of 20 patients with HAART-associated lipoatrophy were randomized to receive either a dietary uridine supplement (36 g three times a day for 10 consecutive days/month) or placebo, for 3 months. Body composition was measured using dual energy X-ray absorptiometry, magnetic resonance imaging and proton spectroscopy. Data are mean ± standard error of mean.ResultsThe mean increases in limb fat (880 ±140 versus 230 ±270 g; P3; PConclusionUridine supplementation significantly and predominantly increased subcutaneous fat mass in lipoatrophic HIV-infected patients during unchanged HAART.
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- 2007
7. Effects of Acquired Obesity on Endothelial Function in Monozygotic Twins*
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Hannele Yki-Järvinen, Kirsi H. Pietiläinen, R Bergholm, Naveed Sattar, Anna-Maija Häkkinen, Jaakko Kaprio, and Aila Rissanen
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Male ,Vasodilator Agents ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Adipose tissue ,Blood Pressure ,030204 cardiovascular system & hematology ,Body Mass Index ,0302 clinical medicine ,Endocrinology ,Heart Rate ,Medicine ,Endothelial dysfunction ,0303 health sciences ,education.field_of_study ,Nutrition and Dietetics ,Forearm ,C-Reactive Protein ,Cholesterol ,Body Composition ,Regression Analysis ,Female ,Adiponectin ,Sodium nitroprusside ,Blood Flow Velocity ,medicine.drug ,Adult ,Nitroprusside ,medicine.medical_specialty ,Population ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,Diseases in Twins ,Humans ,Obesity ,education ,Triglycerides ,030304 developmental biology ,Dose-Response Relationship, Drug ,business.industry ,Cholesterol, HDL ,Cholesterol, LDL ,Twins, Monozygotic ,medicine.disease ,Acetylcholine ,Endothelium, Vascular ,Insulin Resistance ,business ,Dyslipidemia - Abstract
Objective: To determine whether acquired obesity or accompanying metabolic changes such as adiponectin deficiency, insulin resistance, dyslipidemia, or visceral fat are associated, independent of genetic influences, with endothelial dysfunction by studying young adult monozygotic (MZ) twin pairs discordant for obesity. Research Methods and Procedures: Nine obesity-discordant (intra-pair difference in BMI, 3.8 to 10.1 kg/m2) and nine concordant (0 to 2.3 kg/m2) 24- to 27-year-old MZ twin pairs were identified from a population-based FinnTwin16-sample. Endothelial function was measured by blood flow responses to intrabrachial infusions of an endothelium-dependent (acetylcholine) and an endothelium-independent (sodium nitroprusside) vasodilator. Whole body insulin sensitivity was measured using the euglycemic insulin clamp technique, and forearm and body composition were measured with magnetic resonance imaging and DXA. In addition, serum levels of adiponectin, high-sensitivity C-reactive protein, and lipids were determined. Results: The heavier co-twins of the discordant pairs had significantly lower whole body insulin sensitivity than the leaner co-twins. Blood flows/muscle volume during infusions of acetylcholine and sodium nitroprusside were not altered by obesity. However, intra-pair differences in serum adiponectin, intra-abdominal fat, and C-reactive protein were significantly correlated with those in endothelial function. Only the relationship between intra-pair differences in adiponectin and endothelial function persisted in multiple linear regression analysis. Obesity-concordant co-twins had comparable insulin sensitivity and endothelial function. Discussion: In young adult MZ twins discordant for obesity, acquired adiponectin deficiency rather than obesity per se is an independent correlate of endothelial dysfunction.
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- 2006
8. Open Four-Compartment Model in the Measurement of Liver Perfusion1
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Anna-Maija Häkkinen, Juha Halavaara, and Mika Kapanen
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medicine.medical_specialty ,Liver perfusion ,medicine.diagnostic_test ,business.industry ,Blood volume ,Computed tomography ,medicine.anatomical_structure ,Interstitial volume ,Portal blood ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,New zealand white ,Compartment (pharmacokinetics) ,business ,Vein ,Nuclear medicine - Abstract
Rationale and Objectives The goal was to improve informativeness in the determination of liver perfusion with a clinically available iodinated computed tomography (CT) contrast agent by developing open multicompartmental modeling. Materials and Methods Contrast-enhanced functional CT (fCT) examinations were conducted with temporal resolutions of 200–500 msec to 6 New Zealand White rabbits. First, we applied conventional open two-compartment model for the determination of arterial and portal blood flows (F A and F P ), blood and interstitial volume fractions (f b and f i ), and capillary permeability–surface area product (PS) of liver parenchyma. Then, we improved the modeling of vascular physiology by developing three- and open four-compartment models. For comparison, conventional single-compartment model was applied. We determined F A and F P also by using the peak-gradient method. Results Conventional two-compartment model yielded identical fittings with single-compartment model and does not provide unique solutions for f b and f i . The presented open four-compartment model provided F A and F P values of 0.40 ± 0.19 and 1.99 ± 0.57 mL/min/mL (tissue), f b and f i values of 0.30 ± 0.05 and 0.19 ± 0.04 mL/mL (tissue), and PS values of 4.0 ± 1.7 mL/min/mL (tissue). F A and F P are in a good agreement with those derived by using the peak-gradient method. Conclusions With the use of clinical extracellular iodinated CT contrast agent, the presented open four-compartment model provided physiological arterial and portal blood flow values and is also a potential tool in the assessment of blood and interstitial volume fractions and capillary permeability–surface area product. Moreover, the model requires neither measurements from hepatic vein or from other organs nor visual determination of arterial or portal phase.
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- 2005
9. Independent component analysis to proton spectroscopic imaging data of human brain tumours
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Anna-Maija Häkkinen, Anders Paetau, Yrjö Hiltunen, Juhani Pulkkinen, Risto A. Kauppinen, and Nina Lundbom
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Phosphocreatine ,Oligodendroglioma ,Astrocytoma ,computer.software_genre ,Choline ,Nuclear magnetic resonance ,Voxel ,Glioma ,Image Interpretation, Computer-Assisted ,Image Processing, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lactic Acid ,Cell Proliferation ,Aspartic Acid ,medicine.diagnostic_test ,Brain Neoplasms ,business.industry ,Magnetic resonance spectroscopic imaging ,Magnetic resonance imaging ,General Medicine ,Human brain ,Creatine ,medicine.disease ,Lipids ,Magnetic Resonance Imaging ,Independent component analysis ,medicine.anatomical_structure ,Glioblastoma ,Nuclear medicine ,business ,computer ,Algorithms ,Hydrogen - Abstract
In proton magnetic resonance spectroscopic imaging (1H MRSI), the recorded spectra are often linear combinations of spectra from different cell and tissue types within the voxel. This produces problems for data analysis and interpretation. A sophisticated approach is proposed here to handle the complexity of tissue heterogeneity in MRSI data. The independent component analysis (ICA) method was applied without prior knowledge to decompose the proton spectral components that relate to the heterogeneous cell populations with different proliferation and metabolism that are present in gliomas. The ability to classify brain tumours based on IC decomposite spectra was studied by grouping the components with histopathology. To this end, 10 controls and 34 patients with primary brain tumours were studied. The results indicate that ICA may reveal useful information from metabolic profiling for clinical purposes using long echo time MRSI of gliomas.
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- 2005
10. 1H MRS studies in the Finnish boron neutron capture therapy project: Detection of 10B-carrier, l-p-boronophenylalanine-fructose
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Anna-Maija Häkkinen, S. Karjalainen, Mika Kortesniemi, S. Savolainen, Sami Heikkinen, Merja Rasilainen, Aki Kangasmäki, Juhani Collan, T. Huitti, Mauri Kouri, J. Leinonen, A. Lönngren, Marjut Timonen, Leena Kankaanranta, Juha E. Jääskeläinen, and Nina Lundbom
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Adult ,Boron Compounds ,Male ,Magnetic Resonance Spectroscopy ,Gross tumour volume ,medicine.medical_treatment ,chemistry.chemical_element ,Boron Neutron Capture Therapy ,Fructose ,Isotopes of boron ,030218 nuclear medicine & medical imaging ,Dose planning ,Plasma ,03 medical and health sciences ,0302 clinical medicine ,Isotopes ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Resection Cavity ,Boron ,Finland ,Aged ,Brain Neoplasms ,Phantoms, Imaging ,business.industry ,Carcinoma ,General Medicine ,P-boronophenylalanine-fructose ,Radiation therapy ,Neutron capture ,chemistry ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,Radiopharmaceuticals ,Glioblastoma ,business ,Nuclear medicine ,Paranasal Sinus Neoplasms ,Hydrogen - Abstract
This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, l -p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.
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- 2005
11. Five new cases of a recently described leukoencephalopathy with high brain lactate
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Tarja Linnankivi, T Aarimaa, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Taina Autti, Nina Lundbom, Tuomo Kuusi, Hannele Koillinen, Anna-Maija Häkkinen, and Kirsi Sainio
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Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Central nervous system ,Genes, Recessive ,Choline ,030218 nuclear medicine & medical imaging ,Leukoencephalopathy ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Sensory ataxia ,Central Nervous System Diseases ,Evoked Potentials, Somatosensory ,Tremor ,medicine ,Humans ,Spasticity ,Child ,Finland ,Brain Chemistry ,Aspartic Acid ,Pyramidal tracts ,Brain Diseases, Metabolic ,business.industry ,Leukodystrophy ,medicine.disease ,Spinal cord ,Magnetic Resonance Imaging ,Pedigree ,medicine.anatomical_structure ,Spinal Cord ,Muscle Spasticity ,Child, Preschool ,Sensation Disorders ,Disease Progression ,Lactates ,Ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Brain Stem - Abstract
Background: A new leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate was recently defined. The authors describe five new patients with this entity. Methods: Brain MRI was performed in all patients and spinal MRI and proton magnetic resonance spectroscopy ( 1 H-MRS) in four patients. Laboratory examinations ruled out classic leukodystrophies. Results: MRI showed signal abnormalities in the periventricular and deep white matter, in the pyramidal tracts, mesencephalic trigeminal tracts, in the cerebellar connections, and in dorsal columns of the spinal cord. MRS showed decreased N -acetylaspartate and increased lactate in the white matter of all patients. In one patient choline-containing compounds were elevated. A slowly progressive sensory ataxia and tremor manifested at the age of 3 to 16 years and distal spasticity in adolescence. One 13-year-old patient was asymptomatic. Conclusions: A slowly progressive sensory ataxia is a typical feature in this new leukodystrophy. MRS favors a primary axonal degeneration.
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- 2004
12. Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes
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Hannele Yki-Järvinen, Anna-Maija Häkkinen, Sari Mäkimattila, Elena Korsheninnikova, Mirja Tiikkainen, and Tuulikki Nyman
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Type 2 diabetes ,Rosiglitazone ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Triglycerides ,030304 developmental biology ,0303 health sciences ,Adiponectin ,business.industry ,nutritional and metabolic diseases ,Middle Aged ,Lipid Metabolism ,medicine.disease ,Metformin ,3. Good health ,Cholesterol ,Endocrinology ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Gene Expression Regulation ,Liver ,Female ,Thiazolidinediones ,Insulin Resistance ,business ,medicine.drug - Abstract
Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 ± 3 years, fasting plasma glucose 152 ± 9 mg/dl, BMI 30.6 ± 0.8 kg/m2) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA1c, insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 ± 4 vs. 82 ± 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 ± 3 vs. 7 ± 1%, 0 vs. 16 weeks, P = 0.003) but not by metformin (13 ± 3 to 14 ± 3%, NS). Rosiglitazone (16 ± 2 vs. 20 ± 1 ml · kg−1 · min−1, P = 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r = −0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator–activated receptor-γ, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake.
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- 2004
13. High-resolution magic angle spinning and1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3
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Tuomo Polvikoski, Taina Autti, Pirkko Santavuori, Johanna Puranen, Anders Paetau, Beathe Sitter, Tone Frost Bathen, Ursula Sonnewald, Matti Haltia, Jaana Tyynelä, Ingrid S. Gribbestad, and Anna-Maija Häkkinen
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medicine.diagnostic_test ,Chemistry ,Metabolite ,Glutamate receptor ,Magnetic resonance imaging ,medicine.disease ,3. Good health ,030218 nuclear medicine & medical imaging ,Glutamine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Nuclear magnetic resonance ,Biochemistry ,In vivo ,medicine ,Magic angle spinning ,Neuronal ceroid lipofuscinosis ,030217 neurology & neurosurgery ,Ex vivo - Abstract
The neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.3-T high-resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS 1H MRS technique in analysis of autopsy brain tissue. Ex vivo spectra from CLN1 autopsy brain tissue (n = 9) significantly differed from those of the control (n = 9) and CLN3 (n = 5) groups, although no differences were found between the CLN3 and the control groups. Principal component analysis of ex vivo data showed that decreased levels of N-acetylaspartate (NAA), γ-aminobutyric acid (GABA), glutamine, and glutamate as well as increased levels of inositols characterized the CLN1 spectra. Also, the intensity ratio of lipid methylene/methyl protons was decreased in spectra of CLN1 brain tissue compared with CLN3 and control brain tissue. In concordance with the ex vivo data, the in vivo spectra of late-stage patients with CLN1 (n = 3) revealed a dramatic decrease of NAA and a proportional increase of myo-inositol and lipids compared with control subjects. Again, the spectra of patients with CLN3 (n = 13) did not differ from those of controls (n = 15). In conclusion, the ex vivo and in vivo spectroscopic findings were in good agreement within all analyzed groups and revealed significant alterations in metabolite profiles in CLN1 brain tissue but not in CLN3 compared with controls. Furthermore, HR MAS 1H MR spectra facilitated refined detection of neuronal metabolites, including GABA, and composition of lipids in the autopsy brain tissue of NCL patients. © 2004 Wiley-Liss, Inc.
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- 2004
14. Stimulus-induced brain lactate: effects of aging and prolonged wakefulness
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Tarja Porkka-Heiskanen, Nina Lundbom, Anna S. Urrila, Dag Stenberg, Kim Vuori, Sami Heikkinen, Antti Hakkarainen, and Anna-Maija Häkkinen
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Adult ,Aging ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Cognitive Neuroscience ,media_common.quotation_subject ,Stimulus (physiology) ,Vocabulary ,03 medical and health sciences ,Behavioral Neuroscience ,Cognition ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Premovement neuronal activity ,Lactic Acid ,Wakefulness ,Aged ,030304 developmental biology ,media_common ,0303 health sciences ,Cognitive stimulation ,medicine.diagnostic_test ,Verbal Behavior ,Age Factors ,Brain ,General Medicine ,Middle Aged ,Sleep deprivation ,Endocrinology ,Cerebral blood flow ,Anesthesia ,Female ,medicine.symptom ,Functional magnetic resonance imaging ,Psychology ,030217 neurology & neurosurgery ,Vigilance (psychology) - Abstract
Summary Both aging and sleep deprivation disturb the functions of the frontal lobes. Deficits in brain energy metabolism have been reported in these conditions. Neurons use not only glucose but also lactate as their energy substrate. The physiological response to elevated neuronal activity is a transient increase in lactate concentrations in the stimulated area. We have previously shown that cognitive stimulation increases brain lactate. To study the effect of prolonged wakefulness on the lactate response we designed an experiment to assess brain lactate levels during a 40-h sleep deprivation period in young (19–24 years old; n = 13) and in aged (60–68 years old; n = 12) healthy female volunteers. Brain lactate levels were assessed with proton MR-spectroscopy (1H MRS) during the performance of a silent word generation task. The 1H MRS voxel location was individually selected, using functional magnetic resonance imaging, to cover the activated area in the left frontal lobe. The degree of sleepiness was verified using vigilance tests and self-rating scales. In the young alert subjects, the silent word generation test induced a 40% increase in lactate, but during the prolonged wakefulness period this response disappeared. In the aged subjects, the lactate response could not be detected even in the alert state. We propose that the absence of the lactate response may be a sign of malfunctioning of normal brain energy metabolism. The behavioral effects of prolonged wakefulness and aging may arise from this dysfunction.
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- 2004
15. Low-Grade Gliomas and Focal Cortical Developmental Malformations: Differentiation with Proton MR Spectroscopy
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Göran Blomstedt, Heikki Joensuu, Eija Gaily, Kim Vuori, Anna-Maija Häkkinen, Leena Kankaanranta, Marja-Liisa Granström, Nina Lundbom, Leena Valanne, and Anders Paetau
- Subjects
Adult ,Male ,In vivo magnetic resonance spectroscopy ,Pathology ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Adolescent ,Phosphocreatine ,Oligodendroglioma ,Astrocytoma ,Sensitivity and Specificity ,Choline ,Diagnosis, Differential ,Central nervous system disease ,Lesion ,Glioma ,Centrum semiovale ,medicine ,Humans ,Neuroectodermal Tumors, Primitive ,Radiology, Nuclear Medicine and imaging ,Child ,Cerebral Cortex ,Aspartic Acid ,Pilocytic astrocytoma ,business.industry ,Middle Aged ,Creatine ,medicine.disease ,nervous system diseases ,Female ,Epilepsies, Partial ,medicine.symptom ,business ,Nuclear medicine - Abstract
To assess proton magnetic resonance (MR) spectroscopy in differentiating between low-grade gliomas and focal cortical developmental malformations (FCDMs).Eighteen patients with seizures and a cortical brain lesion on MR images were studied with proton MR spectroscopy. A metabolite ratio analysis was performed, and the metabolite signals in the lesion core were compared with those in the contralateral centrum semiovale and in the corresponding brain sites in 18 control subjects to separately obtain the changes in N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine-phosphocreatine (Cr). Ten patients had a low-grade glioma (three, oligodendrogliomas; three, oligoastrocytomas; three, astrocytomas; and one, pilocytic astrocytoma), and eight had FCDM (five, focal cortical dysplasias and three, dysembryoplastic neuroepithelial tumors). Linear discriminant analysis and Student t test were used for statistical comparisons.Loss of NAA and increase of Cho were more pronounced in low-grade gliomas than in FCDMs (NAA, -72% +/- 15 [+/- SD] vs -29% +/- 22, P.001; Cho, 117% +/- 56 vs 21% +/- 66, P.01). Changes in NAA and Cho helped differentiate low-grade gliomas from FCDMs, and changes in Cho and Cr helped differentiate astrocytomas from oligodendrogliomas and oligoastrocytomas. Metabolite NAA/Cho and NAA/Cr ratios helped differentiate low-grade gliomas from FCDMs but did not differentiate glioma subtypes.MR spectroscopy allows distinction between low-grade gliomas and FCDMs and between low-grade glioma subtypes. Metabolite changes are more informative than are metabolite ratios.
- Published
- 2004
16. Body Fat Distribution and Cortisol Metabolism in Healthy Men: Enhanced 5β-Reductase and Lower Cortisol/Cortisone Metabolite Ratios in Men with Fatty Liver
- Author
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Brian R. Walker, Hannele Yki-Järvinen, Jukka Westerbacka, Jonathan R. Seckl, Ruth Andrew, Anna-Maija Häkkinen, Satu Vehkavaara, and Deborah J Wake
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Adipose tissue ,030209 endocrinology & metabolism ,Biology ,Biochemistry ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,3-Oxo-5-alpha-Steroid 4-Dehydrogenase ,Internal medicine ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,medicine ,Humans ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Biochemistry (medical) ,Fatty liver ,Hydroxysteroid Dehydrogenases ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,Cortisone ,Fatty Liver ,Adipose Tissue ,Liver ,Body Composition ,Regression Analysis ,Oxidoreductases ,Body mass index ,Glucocorticoid ,medicine.drug - Abstract
In Cushing's syndrome, cortisol causes fat accumulation in specific sites most likely to be associated with insulin resistance, notably in omental adipose and also perhaps in the liver. In idiopathic obesity, cortisol-metabolizing enzymes may play a key role in determining body fat distribution. Increased regeneration of cortisol from cortisone within adipose by 11beta-hydroxysteroid dehydrogenase (HSD) type 1 (11HSD1) has been proposed to cause visceral fat accumulation, whereas decreased hepatic 11HSD1 may protect the liver from glucocorticoid excess. Increased inactivation of cortisol by 5alpha- and 5beta-reductases in the liver may drive compensatory activation of the hypothalamic-pituitary-adrenal axis, hence increasing adrenal androgens and 'android' central obesity. This study aimed to examine relationships between these enzymes and detailed measurements of body fat distribution. Twenty-five healthy men (age, 22-57 yr; body mass index, 20.6-35.6 kg/m(2)) were recruited from occupational health services. Body composition was assessed by anthropometric measurements, bioimpedance, and cross-sectional abdominal magnetic resonance imaging scans. Liver fat content was assessed by magnetic resonance imaging spectroscopy. Insulin sensitivity was measured in a euglycemic hyperinsulinemic clamp. Cortisol metabolites were measured in a 24-h urine sample by gas chromatography-mass spectrometry. In vivo hepatic 11HSD1 activity was measured by generation of plasma cortisol after an oral dose of cortisone. In vitro 11HSD1 activity and mRNA were measured in 18 subjects who consented to provide abdominal sc adipose biopsies. Indices of obesity (body mass index, whole-body percentage fat, waist/hip ratio) were associated with higher urinary excretion of 5alpha- and 5beta-reduced cortisol metabolites (for percentage fat, P < 0.05 and P < 0.01, respectively) and increased adipose 11HSD1 activity (P < 0.05). Liver fat accumulation was associated with a selective increase in urinary excretion of 5beta-reduced cortisol and cortisone metabolites (P < 0.01) and a lower ratio of cortisol/cortisone metabolites in urine (P < 0.001) but no difference in in vivo cortisone-to-cortisol conversion or in vitro adipose 11HSD1. Higher excretion of 5beta-reduced cortisol metabolites was independently associated with insulin resistance and hypertriglyceridemia. Lower conversion of cortisone to cortisol was associated with lower fasting plasma cortisol (P < 0.01). However, visceral adipose fat mass was not associated with indices of cortisol metabolism; indeed, after adjusting for the effects of whole-body and liver fat, increased visceral fat was associated with lower cortisol metabolite excretion. We conclude that alterations in 11HSD1 and hepatic 5alpha-reductase activity are associated with generalized, rather than central, obesity in humans. Activation of 5beta-reductase in men with fat accumulation in the liver may confound the interpretation of cortisol metabolite excretion when liver fat content is unknown, and may contribute to altered bile acid and cholesterol metabolism in nonalcoholic steatohepatitis.
- Published
- 2003
17. Assessment of vascular physiology of tumorous livers: comparison of two different methods1
- Author
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Juha Halavaara, Mika Kapanen, and Anna-Maija Häkkinen
- Subjects
Liver perfusion ,Pathology ,medicine.medical_specialty ,Liver tumor ,business.industry ,Transit time ,medicine.disease ,Model method ,Modelling methods ,medicine ,Vx2 tumor ,Radiology, Nuclear Medicine and imaging ,New zealand white ,business ,Perfusion - Abstract
Rationale and Objectives. To evaluate liver and liver tumor perfusions by using two different modelling methods: gamma-variate fitting and a single-compartment model. Materials and Methods. 5 New Zealand White rabbits with VX2 tumor implanted into the liver via portal injections were studied. Contrast-enhanced functional CT (fCT) examinations with temporal resolution of 200–500 milliseconds were conducted before tumor inoculation. Thereafter, two or three follow-up studies were conducted. A gamma-variate fitting method was used to determine fractional blood volumes (BV), and a single-compartment model method was used to determine fractional blood volumes (BV), blood flows (BF), and mean transit times (MTT) for normal and tumorous liver regions. Results. For tumorous regions in liver, the gamma-variate fitting and the single-compartment model methods showed statistically significant increases in arterial perfusions (P < 0.01) and decreases in portal perfusions (P < 0.01 with single-compartment model, and P < 0.05 with gamma-variate fitting) when compared with normal liver regions. The single-compartment model showed statistically significant increases (P < 0.01) in MTTs in tumorous regions. In normal liver regions, portal BFs decreased and MTTs increased after tumor inoculation, but the changes were statistically not significant. Conclusion. The gamma-variate fitting and the single-compartment model methods showed definite differences in perfusions between normal and tumorous regions in liver. The single-compartment model showed slightly more distinction and was faster. More importantly, both methods can easily be applied in the clinical environment in the assessment of liver perfusion.
- Published
- 2003
18. Metabolic Imaging of Human Cognition: An fMRI/1H-MRS Study of Brain Lactate Response to Silent Word Generation
- Author
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Tarja Porkka-Heiskanen, Dag Stenberg, Nina Lundbom, Kim Vuori, Sami Heikkinen, Anna S. Urrila, Anna Maija Häkkinen, and Antti Hakkarainen
- Subjects
Adult ,Magnetic Resonance Spectroscopy ,Word generation ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,In vivo ,medicine ,Humans ,Speech ,Premovement neuronal activity ,Lactic Acid ,Cognitive stimulation ,medicine.diagnostic_test ,Metabolic imaging ,Brain ,Magnetic resonance imaging ,Human brain ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Neurology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Proton magnetic resonance spectroscopy (1H-MRS) allows in vivo assessment of the metabolism related to human brain functions. Visual, auditory, tactile, and motor stimuli induce a temporary increase in the brain lactate level, which may act as a rapid source of energy for the activated neurons. The authors studied the metabolism of the frontal lobes during cognitive stimulation and measured local lactate levels with standard 1H-MRS, after localizing the activated area by functional MRI. Lactate levels were monitored while the subjects either silently listed numbers (baseline) or performed a silent word-generation task (stimulus-activation). The cognitive stimulus-activation produced a 50% increase in the brain lactate level in the left inferior frontal gyrus. The results show that metabolic imaging of neuronal activity related to cognition is possible using 1H-MRS.
- Published
- 2003
19. 1H MRS of a boron neutron capture therapy10B-carrier, L-p-boronophenylalanine fructose complex, BPA F: phantom studies at 1.5 and 3.0 T
- Author
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Jyrki Vähätalo, Sami Heikkinen, Marjut Timonen, Anna-Maija Häkkinen, Lundbom N, Aki Kangasmäki, Leena Kankaanranta, and Sauli Savolainen
- Subjects
Boron Compounds ,Magnetic Resonance Spectroscopy ,Materials science ,Phenylalanine ,Boron Neutron Capture Therapy ,Isotopes of boron ,Imaging phantom ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Proton spin crisis ,Computer Simulation ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Radiological and Ultrasound Technology ,Isotope ,Phantoms, Imaging ,Radiotherapy Planning, Computer-Assisted ,Relaxation (NMR) ,Resonance ,Dose-Response Relationship, Radiation ,Radiotherapy Dosage ,Nuclear magnetic resonance spectroscopy ,Models, Theoretical ,Neutron capture ,Feasibility Studies ,Protons ,030217 neurology & neurosurgery - Abstract
The quantification of a BNCT 10B-carrier, L-p-boronophenylalanine-fructose complex (BPA-F), was evaluated using 1H magnetic resonance spectroscopy (1H MRS) with phantoms at 1.5 and 3.0 T. For proper quantification, relaxation times T1 and T2 are needed. While T1 is relatively easy to determine, the determination of T2 of a coupled spin system of aromatic protons of BPA is not straightforward with standard MRS sequences. In addition, an uncoupled concentration reference for aromatic protons of BPA must be used with caution. In order to determine T2, the response of an aromatic proton spin system to the MRS sequence PRESS with various echo times was calculated and the product of the response curve with exponential decay was fitted to the measured intensities. Furthermore, the response curve can be used to correct the intensities, when an uncoupled resonance is used as a concentration reference. BPA was quantified using both phantom replacement and internal water referencing methods with accuracies of +/- 5% and +/- 15%. Our phantom results suggest that in vivo studies on BPA concentration determination will be feasible.
- Published
- 2003
20. Effects of Identical Weight Loss on Body Composition and Features of Insulin Resistance in Obese Women With High and Low Liver Fat Content
- Author
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Hannele Yki-Järvinen, Robert Bergholm, Satu Vehkavaara, Aila Rissanen, Anna-Maija Häkkinen, Mirja Tiikkainen, Kari Teramo, and Marjo Tamminen
- Subjects
Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Saturated fat ,Adipose tissue ,Blood Pressure ,030209 endocrinology & metabolism ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Weight loss ,Internal medicine ,Weight Loss ,Internal Medicine ,medicine ,Humans ,Insulin ,Obesity ,030304 developmental biology ,Glycated Hemoglobin ,0303 health sciences ,Triglyceride ,Cholesterol ,Cholesterol, HDL ,Alanine Transaminase ,Cholesterol, LDL ,gamma-Glutamyltransferase ,Middle Aged ,medicine.disease ,Gestational diabetes ,Endocrinology ,Adipose Tissue ,Liver ,chemistry ,Body Composition ,Body Constitution ,Female ,Insulin Resistance ,medicine.symptom ,Body mass index - Abstract
Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and liver fat (LFAT), as well as features of insulin resistance, in obese women with high versus low LFAT. A total of 23 women with previous gestational diabetes were divided into groups of high (9.4 ± 1.4%) and low (3.3 ± 0.4%) LFAT based on their median LFAT (5%) measured with proton spectroscopy. Both groups were similar with respect to age, BMI, and intra-abdominal and subcutaneous fat. Before weight loss, women with high LFAT had higher fasting serum insulin and triglyceride concentrations than women with low LFAT. At baseline, LFAT correlated with the percent of fat (r = 0.44, P < 0.05) and saturated fat (r = 0.45, P < 0.05) of total caloric intake but not intra-abdominal or subcutaneous fat or fasting serum free fatty acids. Weight loss was similar between the groups (high LFAT −7.4 ± 0.2 vs. low LFAT −7.7 ± 0.3 kg). LFAT decreased from 9.4 ± 1.4 to 4.8 ± 0.7% (P < 0.001) in women with high LFAT and from 3.3 ± 0.4 to 2.0 ± 0.2% (P < 0.001) in women with low LFAT. The absolute decrease in LFAT was significantly higher in women with high than low LFAT (−4.6 ± 1.0 vs. −1.3 ± 0.3%, P < 0.005). The decrease in LFAT was closely correlated with baseline LFAT (r = −0.85, P < 0.001) but not with changes in the volumes of intra-abdominal or subcutaneous fat depots, which decreased similarly in both groups. LFAT appears to be related to the amount of fat in the diet rather than the size of endogenous fat depots in obese women. Women with initially high LFAT lost more LFAT by similar weight loss than those with low LFAT, although both groups lost similar amounts of subcutaneous and intra-abdominal fat. These data suggest that LFAT is regulated by factors other than intra-abdominal and subcutaneous fat. Therefore, LFAT does not appear to simply reflect the size of endogenous fat stores.
- Published
- 2003
21. Fat Accumulation in the Liver Is Associated with Defects in Insulin Suppression of Glucose Production and Serum Free Fatty Acids Independent of Obesity in Normal Men
- Author
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Satu Vehkavaara, Anneli Seppälä-Lindroos, Anna-Maija Häkkinen, Juha Halavaara, Hannele Yki-Järvinen, Jukka Westerbacka, Takashi Goto, and Anssi Sovijärvi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Fasting hyperinsulinemia ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Fatty Acids, Nonesterified ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,High-density lipoprotein ,Reference Values ,Internal medicine ,Blood plasma ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Pancreatic hormone ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Chemistry ,Osmolar Concentration ,Biochemistry (medical) ,VO2 max ,Liter ,Middle Aged ,medicine.disease ,Glucose ,Adipose Tissue ,Liver ,Insulin Resistance - Abstract
We determined whether interindividual variation in hepatic insulin sensitivity could be attributed to variation in liver fat content (LFAT) independent of obesity. We recruited 30 healthy nondiabetic men whose LFAT (determined by proton spectroscopy); intraabdominal, sc, and total (determined by magnetic resonance imaging) fat; and insulin sensitivity of endogenous glucose rate of production (R(a)) and suppression of serum FFA [euglycemic insulin clamp combined with [3-(3)H]glucose (0-300 min); insulin infusion rate, 0.3 mU/kg.min, 120-300 min] were measured. The men were divided into groups of low (mean +/- SD, 1.7 +/- 0.2%) and high (10.5 +/- 2.0%) LFAT based on their median fat content. The low and high LFAT groups were comparable with respect to age (44 +/- 2 vs. 42 +/- 2 yr), body mass index (25 +/- 1 vs. 26 +/- 1 kg/m(2) ), waist to hip ratio (0.953 +/- 0.013 vs. 0.953 +/- 0.013), maximal oxygen uptake (35.6 +/- 1.5 vs. 33.5 +/- 1.5 ml/kg.min), and intraabdominal, sc, and total fat. The high compared with the low LFAT group had several features of insulin resistance, including fasting hyperinsulinemia (7.3 +/- 0.6 vs. 5.3 +/- 0.6 mU/liter; P < 0.02, high vs. low LFAT) hypertriglyceridemia (1.4 +/- 0.2 vs. 0.9 +/- 0.1 mmol/liter; P < 0.02), a low high density lipoprotein (HDL) cholesterol concentration (1.4 +/- 0.1 vs. 1.6 +/- 0.1 mmol/liter; P < 0.05), and a higher ambulatory 24-h systolic blood pressure (130 +/- 3 vs. 122 +/- 3 mm Hg; P < 0.05). Basal glucose R(a) and serum FFA were comparable between the groups, whereas insulin suppression of glucose R(a) [51 +/- 8 vs. 20 +/- 12 mg/m(2).min during 240-300 min (P < 0.05) or -55 +/- 7 vs. -85 +/- 12% below basal (P < 0.05, high vs. low LFAT)] and of serum FFA (299 +/- 33 vs. 212 +/- 13 micromol/liter; 240-300 min; P < 0.02) were impaired in the high compared with the low LFAT group. Insulin stimulation of glucose Rd were comparable in the men with high LFAT (141 +/- 12 mg/m(2).min) and those with low LFAT (156 +/- 14 mg/m(2).min; P = NS). Fat accumulation in the liver is, independent of body mass index and intraabdominal and overall obesity, characterized by several features of insulin resistance in normal weight and moderately overweight subjects.
- Published
- 2002
22. Quantification of Human Brain Metabolites from in Vivo1H NMR Magnitude Spectra Using Automated Artificial Neural Network Analysis
- Author
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Nina Lundbom, Juhani Pulkkinen, Jouni Kaartinen, Risto A. Kauppinen, Yrjö Hiltunen, and Anna Maija Häkkinen
- Subjects
Nuclear and High Energy Physics ,Magnetic Resonance Spectroscopy ,brain metabolites ,Metabolite ,Biophysics ,Analytical chemistry ,simulated spectra ,Biochemistry ,Spectral line ,Choline ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,NMR spectroscopy ,0302 clinical medicine ,Nuclear magnetic resonance ,In vivo ,medicine ,Humans ,metabolites ,Brain Chemistry ,1H nuclear magnetic resonance spectroscopy ,Aspartic Acid ,Artificial neural network ,Chemistry ,Brain ,Nuclear magnetic resonance spectroscopy ,Human brain ,Condensed Matter Physics ,quantification ,medicine.anatomical_structure ,Creatinine ,Magnitude (astronomy) ,Proton NMR ,Neural Networks, Computer ,artificial neural network ,030217 neurology & neurosurgery - Abstract
Long echo time (TE=270 ms) in vivo proton NMR spectra resembling human brain metabolite patterns were simulated for lineshape fitting (LF) and quantitative artificial neural network (ANN) analyses. A set of experimental in vivo 1 H NMR spectra were first analyzed by the LF method to match the signal-to-noise ratios and linewidths of simulated spectra to those in the experimental data. The performance of constructed ANNs was compared for the peak area determinations of choline-containing compounds (Cho), total creatine (Cr), and N-acetyl aspartate (NAA) signals using both manually phase-corrected and magnitude spectra as inputs. The peak area data from ANN and LF analyses for simulated spectra yielded high correlation coefficients demonstrating that the peak areas quantified with ANN gave similar results as LF analysis. Thus, a fully automated ANN method based on magnitude spectra has demonstrated potential for quantification of in vivo metabolites from long echo time spectroscopic imaging.
- Published
- 2002
23. Proton Spectroscopic Imaging Shows Abnormalities in Glial and Neuronal Cell Pools in Frontal Lobe Epilepsy
- Author
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Anna-Maija Häkkinen, Leena Valanne, Eija Gaily, Ritva Paetau, Lundbom N, K. Vuori, Elina Liukkonen, Marja-Liisa Granström, and Jagath C. Rajapakse
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Adolescent ,Phosphocreatine ,Epilepsy, Frontal Lobe ,Functional Laterality ,Central nervous system disease ,White matter ,chemistry.chemical_compound ,Epilepsy ,Cerebrospinal fluid ,Parietal Lobe ,Biopsy ,Humans ,Medicine ,Child ,Monitoring, Physiologic ,Neurons ,Aspartic Acid ,medicine.diagnostic_test ,business.industry ,Brain ,Videotape Recording ,Electroencephalography ,Creatine ,medicine.disease ,Magnetic Resonance Imaging ,Frontal Lobe ,Functional imaging ,medicine.anatomical_structure ,Neurology ,Frontal lobe ,chemistry ,Child, Preschool ,Chronic Disease ,Female ,Neurology (clinical) ,business ,Neuroglia - Abstract
Summary: Purpose: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. Methods: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. Results: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. Conclusions: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a “noninvasive biopsy” in epileptogenic lesions.
- Published
- 2001
24. Two brothers with macrocephaly, progressive cerebral atrophy and abnormal white matter, severe mental retardation, and Lennox-Gastaut spectrum type epilepsy: An inherited encephalopathy of childhood?
- Author
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Pekka Nokelainen, Raili Raininko, Hannu Heiskala, Taina Autti, Anna-Maija Häkkinen, Kari Wirtavuori, and Jonathan Flint
- Subjects
Male ,Pathology ,medicine.medical_specialty ,X Chromosome ,Fetal alcohol syndrome ,Corpus callosum ,Fourth ventricle ,Nuclear Family ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Intellectual Disability ,medicine ,Humans ,Abnormalities, Multiple ,Genetics (clinical) ,Cerebral atrophy ,0303 health sciences ,Epilepsy ,business.industry ,030305 genetics & heredity ,Macrocephaly ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,Hypoplasia ,Pedigree ,Palpebral fissure ,medicine.anatomical_structure ,Fetal Alcohol Spectrum Disorders ,Karyotyping ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Two brothers with severe mental retardation of unknown origin were found to share several physical anomalies, including large round head, small concave nose, downslanted palpebral fissures, and gingival hyperplasia. In addition to relative macrocephaly, magnetic resonance imaging (MRI) showed severe cerebral atrophy, especially fronto-temporally. The brothers also had a thin corpus callosum and atrophic caudate nuclei. The reduced white matter showed patchy periventricular signal intensity changes. The lateral and third ventricles were large, but the fourth ventricle was of normal size. The boys had large cisterna magna, communicating widely with the fourth ventricle, but no vermian hypoplasia. Both boys had Lennox-Gastaut spectrum type epilepsy. No chromosomal anomalies were found, despite the suggestive clinical picture. Some of the clinical findings resembled fetal alcohol effects/fetal alcohol syndrome (FAE/FAS), which was also suggested by history. Current diagnostic criteria for FAE/FAS, however, excluded full-blown FAS in these cases and failed to explain the entire clinical picture in the boys. We argue that these boys had an unidentified inherited syndrome, possibly modified by fetal alcohol exposure.
- Published
- 2001
25. 3D spin-lock imaging of human gliomas
- Author
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Usama Abo Ramadan, Juha Jääskeläinen, Teemu K. Peltonen, Raimo Sepponen, Jukka I. Tanttu, Anna Maija Häkkinen, Hannu J. Aronen, and Antti T. Markkola
- Subjects
Adult ,Gadolinium DTPA ,Male ,media_common.quotation_subject ,Biomedical Engineering ,Biophysics ,Contrast Media ,Imaging phantom ,030218 nuclear medicine & medical imaging ,Central nervous system disease ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Glioma ,Image Processing, Computer-Assisted ,medicine ,Humans ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Bovine serum albumin ,Aged ,media_common ,medicine.diagnostic_test ,biology ,Brain Neoplasms ,Phantoms, Imaging ,Chemistry ,Pulse (signal processing) ,business.industry ,Brain ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,Contrast medium ,biology.protein ,Female ,Nuclear medicine ,business ,030217 neurology & neurosurgery - Abstract
We investigated whether the simultaneous use of paramagnetic contrast medium and 3D on-resonance spin lock (SL) imaging could improve the contrast of enhancing brain tumors at 0.1 T. A phantom containing serial concentrations of gadopentetate dimeglumine (Gd-DTPA) in cross-linked bovine serum albumin (BSA) was imaged. Eleven patients with histologically verified glioma were also studied. T1-weighted 3D gradient echo images with and without SL pulse were acquired before and after a Gd-DTPA injection. SL effect, contrast, and contrast-to-noise ratio (CNR) were calculated for each patient. In the glioma patients, the SL effect was significantly smaller in the tumor than in the white and gray matter both before (p = 0.001, p = 0.025, respectively), and after contrast medium injection (p < 0.001, p < 0.001, respectively). On post-contrast images, SL imaging significantly improved tumor contrast (p = 0.001) whereas tumor CNR decreased slightly (p = 0.024). The combined use of SL imaging and paramagnetic Gd-DTPA contrast agent offers a modality for improving tumor contrast in magnetic resonance imaging (MRI) of enhancing brain tumors. 3D gradient echo SL imaging has also shown potential to increase tissue characterization properties of MR imaging of human gliomas.
- Published
- 1999
26. Association of intramyocellular, intraperitoneal and liver fat with glucose tolerance in severely obese adolescents
- Author
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Koen Van Leemput, Tero Saukkonen, Antti Hakkarainen, Marita Lipsanen-Nyman, Anna-Maija Häkkinen, Sami Heikkinen, and Nina Lundbom
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Muscle Fibers, Skeletal ,Abdominal Fat ,030209 endocrinology & metabolism ,Relative weight ,030204 cardiovascular system & hematology ,Secondary care ,Impaired glucose tolerance ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Liver fat ,Glucose Intolerance ,medicine ,Abdominal fat ,Humans ,Obesity ,Child ,2. Zero hunger ,business.industry ,Age Factors ,General Medicine ,medicine.disease ,Fatty Liver ,Cross-Sectional Studies ,Body Composition ,Female ,business ,Body mass index ,Homeostasis - Abstract
ObjectiveImpaired glucose tolerance (IGT) is common among obese adolescents. The aim of the present study was to investigate the association between glucose tolerance and intramyocellular, intra-abdominal and liver fat in adolescents presenting with early-onset severe obesity.Design and methodsWe studied 21 adolescents (mean age 13.5 years, range 11.5–15.9 years) referred to secondary care due to severe obesity (relative weight for height >+60% or body mass index >98th percentile for age and sex, before the age of 10 years) and their eight non-obese siblings (mean age 14.4 years, range 11.8–16.7 years). All subjects underwent oral glucose tolerance tests, followed by magnetic resonance spectroscopy (MRS) to measure the intramyocellular fat content in mainly oxidative soleus and mainly glycolytic tibialis anterior muscles. MRS was also used to measure liver fat. Abdominal fat (subcutaneous, intraperitoneal and retroperitoneal) was measured using MR imaging.ResultsCompared with their non-obese siblings, the obese adolescents had increased fat deposition in all anatomic locations studied. Eight obese adolescents had IGT, and they also had increased intramyocellular fat in the soleus (P=0.03) and increased intraperitoneal fat (P=0.04) compared with obese subjects with normal glucose tolerance (NGT). In contrast, no significant difference was seen between obese adolescents with NGT and IGT in liver fat (P=0.9) or intramyocellular fat in the tibialis anterior (P=0.13). In logistic regression analysis, increased soleus intramyocellular fat and intraperitoneal fat were significant predictors of IGT.ConclusionsIGT in obese adolescents is associated with increased intramyocellular and intraperitoneal fat rather than liver fat.
- Published
- 2010
27. 13C CP-MAS solid-state NMR and multinuclear solution state magnetic resonance spectra of some sulphur amides and carboxamides
- Author
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Anna-Maija Häkkinen and P. Ruostesuo
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,medicine.drug_class ,Chemical shift ,Resonance ,Carboxamide ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Carbon-13 NMR ,010402 general chemistry ,01 natural sciences ,3. Good health ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Solid-state nuclear magnetic resonance ,medicine ,Physical chemistry ,Organic chemistry ,General Materials Science ,Thioacetamide ,Thioamide - Abstract
The 13C NMR chemical shifts in the solution and in the solid state and those of 15N and 17O and the line widths of the 14N and 17O resonance signals in the solution state were determined for carboxamides, aliphatic and aromatic sulphon- and sulphin-amides and a thioamide (thioacetamide).
- Published
- 1991
28. Comparison of liver perfusion parameters studied with conventional extravascular and experimental intravascular CT contrast agents
- Author
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Anna-Maija Häkkinen, Juha Halavaara, and Mika Kapanen
- Subjects
Liver perfusion ,Blood pool agent ,Iohexol ,chemistry.chemical_element ,Contrast Media ,Iodine ,Diatrizoate ,Bolus (medicine) ,medicine.artery ,Medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Liver blood flow ,Aorta ,Blood Volume ,business.industry ,chemistry ,Liver ,Rabbits ,Nuclear medicine ,business ,Tomography, X-Ray Computed ,Perfusion ,medicine.drug ,Liver Circulation - Abstract
Rationale and Objectives To compare liver perfusion parameters obtained by using an extravascular contrast agent and a blood-pool agent. Materials and Methods Fifteen rabbits were imaged with a continuous 40-second single-slice computed tomography acquisition after a bolus injection of contrast agent (physiologic bolus duration 4–5 seconds, extravascular iohexol, n = 7; experimental nanoparticulated blood-pool agent WIN8883, n = 8). Time-density curves were generated for the aorta, portal vein, and liver. From the curves, arterial, portal, and total blood flows and hepatic perfusion index (HPI, arterial-to-total perfusion ratio) were determined by using two commonly applied fundamentally different analyzing methods: the single-compartment model and the peak gradient (PG) method. Also, the gamma variate fitting method was used. Results By using the single-compartment model, the obtained HPI and total blood flow were 0.14 ± 0.04 and 2.29 ± 0.40 (mL/min/mLtissue) for WIN8883, and 0.15 ± 0.06 (P = .54) and 4.60 ± 1.14 (mL/min/mLtissue) (P = .0002) for iohexol, respectively. With the PG, HPI and total blood flow were 0.15 ± 0.08 and 1.27 ± 0.24 (mL/min/mLtissue) for WIN8883, and 0.20 ± 0.06 (P = .12) and 2.11 ± 0.25 (mL/min/mLtissue) (P = .00002) for iohexol, respectively. With the blood pool agent, similar contrast enhancement to the conventional agent was achieved with about 36% reduced dosage of iodine per body weight (mg I/kg). Conclusions HPI was found to be quite insensitive to different contrast agent types and analyzing methods. However, the arterial, portal and total liver blood flow values strongly depend on contrast agent type and modeling method.
- Published
- 2007
29. Preliminary findings of proton magnetic resonance spectroscopy in occipital cortex during sleep deprivation
- Author
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Sami Heikkinen, Tuomo Kuusi, Dag Stenberg, Tarja Porkka-Heiskanen, Outi Huhdankoski, Nina Lundbom, Anna S. Urrila, Antti Hakkarainen, and Anna-Maija Häkkinen
- Subjects
Adult ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Time Factors ,Photic Stimulation ,Central nervous system ,Neuroscience (miscellaneous) ,Choline ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Circadian rhythm ,Wakefulness ,Neurotransmitter ,030304 developmental biology ,0303 health sciences ,Sleep disorder ,Aspartic Acid ,Electroencephalography ,medicine.disease ,Creatine ,3. Good health ,Cortex (botany) ,Psychiatry and Mental health ,Sleep deprivation ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Sleep Deprivation ,Female ,Occipital Lobe ,medicine.symptom ,Protons ,Energy Metabolism ,030217 neurology & neurosurgery - Abstract
Proton magnetic resonance spectroscopy ((1)H MRS) has revealed biochemical alterations in various psychiatric disorders. Changes in brain metabolites may be caused not only by the disease's progression or response to treatment, but also by physiological variability. The aim of this study was to use (1)H MRS to assess the effects of specific short-term physiological states on major metabolites. Eight healthy women underwent (1)H MRS at the beginning and end of a 40-h period of sleep deprivation. The ratios of N-acetyl-aspartate (NAA), total creatine (tCr), and choline-containing compounds (Cho) to water (H(2)O) were determined from the occipital cortex during both baseline and photic stimulation conditions. During sleep deprivation, NAA/H(2)O decreased by 7% and Cho/H(2)O by 12%. Photic stimulation had no effect on the measured metabolites in the alert state, but in the sleep-deprived state the level of Cho/H(2)O increased during neuronal activation. The results suggest that NAA/H(2)O and Cho/H(2)O may depend on the state of alertness.
- Published
- 2005
30. Overproduction of large VLDL particles is driven by increased liver fat content in man
- Author
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Satu Vehkavaara, Jan Borén, Hannele Yki-Järvinen, Chris J. Packard, Aino Soro-Paavonen, Muriel J. Caslake, Martin Adiels, Marja-Riitta Taskinen, Jukka Westerbacka, Sven-Olof Olofsson, and Anna-Maija Häkkinen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Fat content ,Endocrinology, Diabetes and Metabolism ,Plasma adiponectin ,Lipoproteins, VLDL ,chemistry.chemical_compound ,Internal medicine ,Liver fat ,Internal Medicine ,medicine ,Humans ,Overproduction ,Aged ,Apolipoproteins B ,biology ,Triglyceride ,Human physiology ,Middle Aged ,Fatty Liver ,Endocrinology ,chemistry ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production.A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI.Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB.We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
- Published
- 2005
31. Metabolite phantom correction of the nonuniform volume-selection profiles in MR spectroscopic imaging: application to temporal lobe epilepsy
- Author
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J O Jesper, Lundbom, Kim E, Vuori, Eija K, Gaily, R I Marja-Liisa, Granström, Göran C, Blomstedt, Anna-Maija, Häkkinen, Sami M, Heikkinen, and Nina M I, Lundbom
- Subjects
Adult ,Male ,Magnetic Resonance Spectroscopy ,Adolescent ,Epilepsy, Temporal Lobe ,Humans ,Brain ,Female ,Middle Aged ,Child ,behavioral disciplines and activities ,nervous system diseases - Abstract
BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.
- Published
- 2005
32. Open four-compartment model in the measurement of liver perfusion
- Author
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Mika K, Kapanen, Juha T, Halavaara, and Anna-Maija, Häkkinen
- Subjects
Blood Volume ,Blood Volume Determination ,Models, Cardiovascular ,Contrast Media ,Reproducibility of Results ,Sensitivity and Specificity ,Portal System ,Liver ,Animals ,Radiographic Image Interpretation, Computer-Assisted ,Computer Simulation ,Rabbits ,Blood Flow Velocity ,Liver Circulation - Abstract
The goal was to improve informativeness in the determination of liver perfusion with a clinically available iodinated computed tomography (CT) contrast agent by developing open multicompartmental modeling.Contrast-enhanced functional CT (fCT) examinations were conducted with temporal resolutions of 200-500 msec to 6 New Zealand White rabbits. First, we applied conventional open two-compartment model for the determination of arterial and portal blood flows (FA and FP), blood and interstitial volume fractions (fb and fi), and capillary permeability-surface area product (PS) of liver parenchyma. Then, we improved the modeling of vascular physiology by developing three- and open four-compartment models. For comparison, conventional single-compartment model was applied. We determined FA and FP also by using the peak-gradient method.Conventional two-compartment model yielded identical fittings with single-compartment model and does not provide unique solutions for fb and fi. The presented open four-compartment model provided FA and FP values of 0.40 +/- 0.19 and 1.99 +/- 0.57 mL/min/mL (tissue), fb and fi values of 0.30 +/- 0.05 and 0.19 +/- 0.04 mL/mL (tissue), and PS values of 4.0 +/- 1.7 mL/min/mL (tissue). FA and FP are in a good agreement with those derived by using the peak-gradient method.With the use of clinical extracellular iodinated CT contrast agent, the presented open four-compartment model provided physiological arterial and portal blood flow values and is also a potential tool in the assessment of blood and interstitial volume fractions and capillary permeability-surface area product. Moreover, the model requires neither measurements from hepatic vein or from other organs nor visual determination of arterial or portal phase.
- Published
- 2005
33. Decreased cerebellar total creatine in episodic ataxia type 2: a 1H MRS study
- Author
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Sami Heikkinen, Markus Färkkilä, M. Wessman, Mari A. Kaunisto, Nina Lundbom, Anna-Maija Häkkinen, Hanna Harno, and Mikko Kallela
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cerebellum ,Magnetic Resonance Spectroscopy ,Adolescent ,Nystagmus ,Biology ,Creatine ,medicine.disease_cause ,Nystagmus, Pathologic ,Choline ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Spinocerebellar Ataxias ,Child ,Mutation ,Aspartic Acid ,Cerebellar ataxia ,Calcium channel ,Total creatine ,Dysarthria ,Episodic ataxia type 2 ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Lactates ,Female ,Neurology (clinical) ,Calcium Channels ,RNA Splice Sites ,medicine.symptom - Abstract
Episodic ataxia type 2 (EA2) affects mainly the cerebellum via mutations in the CACNA1A gene. The authors used proton MR spectroscopy to examine cerebellar and thalamic metabolism of nine mostly nonataxic EA2 family members (all with proven CACNA1A mutation) and nine healthy control subjects. Cerebellar total creatine was lower in the patient group (p = 0.005) than in control subjects, possibly reflecting an early sign of calcium channel dysfunction in EA2.
- Published
- 2005
34. Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury
- Author
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Sari Mäkimattila, Oili Salonen, Sami Heikkinen, Anna-Maija Häkkinen, Risto O. Roine, Nina Lundbom, Kim Vuori, Markku Kaste, Kirsi Malmberg-Ceder, Paula Summanen, and Hannele Yki-Järvinen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Thalamus ,030218 nuclear medicine & medical imaging ,Nephropathy ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Type 1 diabetes ,Cell adhesion molecule ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Pathophysiology ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 1 ,Neurology ,Brain Injuries ,Hyperglycemia ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Retinopathy - Abstract
Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the frontal cortex, thalamus, and posterior frontal white matter. There was no change in N-acetyl–containing compounds (NA), but choline-containing compounds (Cho) were increased in the white matter and in the thalamus; myo-inositol was increased in the white matter, glucose excess was found in all brain, and water intensity was increased in the cortical voxel in the patients. Calculated lifetime glycemic exposure correlated inversely with Cho and NA in white matter and with Cho in thalamus. Concentrations of soluble intercellular adhesion molecules and vascular cell adhesion molecules were increased in the patients. In conclusion, in patients with type 1 diabetes, the increase in adhesion molecules and an association between altered brain metabolites and glycemic exposure suggest the presence of a vascularly mediated, progressive metabolic disturbance in the brain.
- Published
- 2004
35. Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins
- Author
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Satu Vehkavaara, Aila Rissanen, Jussi Sutinen, Jaakko Kaprio, Anna-Maija Häkkinen, Hannele Yki-Järvinen, Kirsi H. Pietiläinen, Jukka Westerbacka, and Sari Mäkimattila
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Intra-Abdominal Fat ,Physiology ,Endocrinology, Diabetes and Metabolism ,Monozygotic twin ,030209 endocrinology & metabolism ,Biology ,Statistics, Nonparametric ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Absorptiometry, Photon ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Obesity ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Fatty liver ,Twins, Monozygotic ,Glucose clamp technique ,medicine.disease ,Twin study ,Magnetic Resonance Imaging ,Fatty Liver ,Endocrinology ,Adipose Tissue ,Body Composition ,Glucose Clamp Technique ,Female ,Insulin Resistance ,Body mass index - Abstract
We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0–33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat ( r = 0.82, P < 0.001) and liver fat ( r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal ( r = 0.60, P = 0.008), intra-abdominal ( r = 0.75, P = 0.0001) and liver ( r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal ( r = −0.72, P = 0.001) and intra-abdominal ( r = −0.55, P = 0.015) but not liver ( r = −0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.
- Published
- 2004
36. High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3
- Author
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Beathe, Sitter, Taina, Autti, Jaana, Tyynelä, Ursula, Sonnewald, Tone F, Bathen, Johanna, Puranen, Pirkko, Santavuori, Matti J, Haltia, Anders, Paetau, Tuomo, Polvikoski, Ingrid S, Gribbestad, and Anna-Maija, Häkkinen
- Subjects
Adult ,Brain Chemistry ,Male ,Neurons ,Analysis of Variance ,Aspartic Acid ,Magnetic Resonance Spectroscopy ,Membrane Glycoproteins ,Adolescent ,Glutamine ,Brain ,Glutamic Acid ,Membrane Proteins ,Creatine ,Choline ,Neuronal Ceroid-Lipofuscinoses ,Child, Preschool ,Humans ,Female ,Thiolester Hydrolases ,Child ,Inositol ,gamma-Aminobutyric Acid ,Molecular Chaperones - Abstract
The neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.3-T high-resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS (1)H MRS technique in analysis of autopsy brain tissue. Ex vivo spectra from CLN1 autopsy brain tissue (n = 9) significantly differed from those of the control (n = 9) and CLN3 (n = 5) groups, although no differences were found between the CLN3 and the control groups. Principal component analysis of ex vivo data showed that decreased levels of N-acetylaspartate (NAA), gamma-aminobutyric acid (GABA), glutamine, and glutamate as well as increased levels of inositols characterized the CLN1 spectra. Also, the intensity ratio of lipid methylene/methyl protons was decreased in spectra of CLN1 brain tissue compared with CLN3 and control brain tissue. In concordance with the ex vivo data, the in vivo spectra of late-stage patients with CLN1 (n = 3) revealed a dramatic decrease of NAA and a proportional increase of myo-inositol and lipids compared with control subjects. Again, the spectra of patients with CLN3 (n = 13) did not differ from those of controls (n = 15). In conclusion, the ex vivo and in vivo spectroscopic findings were in good agreement within all analyzed groups and revealed significant alterations in metabolite profiles in CLN1 brain tissue but not in CLN3 compared with controls. Furthermore, HR MAS 1H MR spectra facilitated refined detection of neuronal metabolites, including GABA, and composition of lipids in the autopsy brain tissue of NCL patients.
- Published
- 2004
37. Women and men have similar amounts of liver and intra-abdominal fat, despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk
- Author
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Anna-Maija Häkkinen, Marjo Tamminen, Jukka Westerbacka, Hannele Yki-Järvinen, Mirja Tiikkainen, A. Cornér, Jenny Fredriksson, and Satu Vehkavaara
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Intra-Abdominal Fat ,Endocrinology, Diabetes and Metabolism ,Biology ,White People ,chemistry.chemical_compound ,Insulin resistance ,NEFA ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Abdomen ,Internal Medicine ,medicine ,Humans ,Skin ,Sweden ,Sex Characteristics ,Adiponectin ,Triglyceride ,Cholesterol ,Middle Aged ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,Adipose Tissue ,chemistry ,Cardiovascular Diseases ,Intercellular Signaling Peptides and Proteins ,Female ,Insulin Resistance ,Biomarkers - Abstract
Fat accumulation in the liver has been shown to be closely correlated with hepatic insulin resistance and features of insulin resistance, also independently of body weight. It remains to be established how fat in the liver correlates with that in other depots, and whether any association differs between men and women.Liver fat (assessed using proton spectroscopy), intra-abdominal and subcutaneous fat (measured using magnetic resonance imaging) and markers of insulin resistance, including serum adiponectin, were determined in 132 non-diabetic subjects: 66 men (age 41+/-1 years) and 66 women (age 42+/-1 years).Although the women had almost twice as much subcutaneous fat as the men (5045+/-207 vs 2610+/-144 cm3, p0.0001), amounts of intra-abdominal fat (1305+/-80 vs 1552+/-111 cm3, NS) and liver fat (6.7+/-0.8 vs 8.9+/-1.2%, NS) were similar. In this study, no sex differences were observed with respect to serum insulin, adiponectin, triglyceride and HDL cholesterol concentrations. Of all measures of body composition, liver fat was best correlated with serum insulin (r=0.58, p0.001), with no difference observed between men and women. Serum adiponectin was inversely correlated with liver fat content (r=-0.21, p0.05). Multiple linear regression analysis revealed that intra-abdominal fat was significantly associated with liver fat, independently of serum adiponectin and subcutaneous fat. Liver fat, but not intra-abdominal fat, significantly explained the variation in serum insulin concentrations.Intra-abdominal fat is independently associated with liver fat, whereas subcutaneous fat is not. Liver fat, but not intra-abdominal fat, is independently associated with serum insulin. Men and women with similar amounts of intra-abdominal and liver fat do not exhibit sex differences in markers of insulin resistance (serum insulin, triglycerides, HDL cholesterol and adiponectin).
- Published
- 2004
38. Assessment of vascular physiology of tumorous livers: comparison of two different methods
- Author
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Mika K, Kapanen, Juha T, Halavaara, and Anna-Maija, Häkkinen
- Subjects
Perfusion ,Portal System ,Liver Neoplasms, Experimental ,Liver ,Animals ,Contrast Media ,Rabbits ,Tomography, X-Ray Computed ,Algorithms - Abstract
To evaluate liver and liver tumor perfusions by using two different modelling methods: gamma-variate fitting and a single-compartment model.5 New Zealand White rabbits with VX2 tumor implanted into the liver via portal injections were studied. Contrast-enhanced functional CT (fCT) examinations with temporal resolution of 200-500 milliseconds were conducted before tumor inoculation. Thereafter, two or three follow-up studies were conducted. A gamma-variate fitting method was used to determine fractional blood volumes (BV), and a single-compartment model method was used to determine fractional blood volumes (BV), blood flows (BF), and mean transit times (MTT) for normal and tumorous liver regions.For tumorous regions in liver, the gamma-variate fitting and the single-compartment model methods showed statistically significant increases in arterial perfusions (P0.01) and decreases in portal perfusions (P0.01 with single-compartment model, and P0.05 with gamma-variate fitting) when compared with normal liver regions. The single-compartment model showed statistically significant increases (P0.01) in MTTs in tumorous regions. In normal liver regions, portal BFs decreased and MTTs increased after tumor inoculation, but the changes were statistically not significant.The gamma-variate fitting and the single-compartment model methods showed definite differences in perfusions between normal and tumorous regions in liver. The single-compartment model showed slightly more distinction and was faster. More importantly, both methods can easily be applied in the clinical environment in the assessment of liver perfusion.
- Published
- 2003
39. MnDPDP-enhanced magnetization transfer MR imaging: implications for effective liver imaging
- Author
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Anna-Maija Häkkinen, Hannu J. Aronen, Juha Halavaara, Antti T. Markkola, and Usama Abo-Ramadan
- Subjects
medicine.diagnostic_test ,biology ,Chemistry ,Phantoms, Imaging ,Liver Diseases ,Biomedical Engineering ,Biophysics ,Contrast Media ,Magnetic resonance imaging ,Image enhancement ,Image Enhancement ,Mr imaging ,Magnetic Resonance Imaging ,Imaging phantom ,Nuclear magnetic resonance ,Liver ,Pyridoxal Phosphate ,medicine ,biology.protein ,Humans ,Radiology, Nuclear Medicine and imaging ,Magnetization transfer ,Bovine serum albumin ,Edetic Acid ,Liver imaging - Abstract
The benefit of combining magnetization transfer (MT) MR imaging technique with liver-specific contrast agent manganese dipyridoxyldiphosphate (MnDPDP) was assessed in our experimental investigation. The study was accomplished by imaging a phantom containing serial concentrations of MnDPDP in cross-linked bovine serum albumin (BSA) with various protein concentrations. A 0.1T clinical MR imager with different parameters for MT and conventional MR sequences were used. The combination of an offset frequency of 8 kHz and an amplitude of 25 microT produced nearly maximal MT effect for all protein samples either without MnDPDP or with different MnDPDP concentrations. With long TRs (TR > 200 ms) MT dramatically improved CNR in conjunction with MnDPDP. With short TRs, the gain in CNR with MT was negligible. However, long TRs with increased number of images are beneficial in liver imaging. We conclude that MT like preparation pulse is useful when paramagnetic contrast agents such as MnDPDP are employed.
- Published
- 2003
40. Quantification of Human Brain Metabolites from In Vivo 1H NMR Magnitude Spectra Using Self-Organising Maps
- Author
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Risto A. Kauppinen, Yrjö Hiltunen, Mika Lappalainen, Juhani Pulkkinen, Nina Lundbom, and Anna-Maija Häkkinen
- Subjects
medicine.diagnostic_test ,Computer science ,business.industry ,Magnetic resonance spectroscopic imaging ,Magnetic resonance imaging ,Nuclear magnetic resonance spectroscopy ,Human brain ,Self organising maps ,Spectral line ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine.anatomical_structure ,In vivo ,medicine ,Proton NMR ,Artificial intelligence ,business ,030217 neurology & neurosurgery - Abstract
The self-organising map (SOM) analysis has been successfully applied in many fields of research and it is a potential tool also for analysis of magnetic resonance spectroscopy (MRS) data. In this paper we demonstrate that SOM-based analysis, can be applied for automated MRS data quantification. To this end, a set of experimental long echo time (TE=270 ms) in vivo 1H MRS spectra were initially analysed by the lineshape fitting (LF) method to find out simulated spectra mathing to the experimental data. The results from simulated data sets show that clinically relevant metabolite quantification from human brain MRS can be obtained with the SOM analysis.
- Published
- 2003
41. Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes
- Author
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Satu Vehkavaara, Aila Rissanen, Anna-Maija Häkkinen, Mirja Tiikkainen, Robert Bergholm, Hannele Yki-Järvinen, Kari Teramo, Marjo Tamminen, and Juha Halavaara
- Subjects
Adult ,Blood Glucose ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Blood Pressure ,030204 cardiovascular system & hematology ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Heart Rate ,Pregnancy ,Internal medicine ,Liver fat ,medicine ,Humans ,Insulin ,Total fat ,Obesity ,Triglycerides ,2. Zero hunger ,Triglyceride ,business.industry ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Gestational diabetes ,Diabetes, Gestational ,chemistry ,Adipose Tissue ,Liver ,Body Composition ,Glucose Clamp Technique ,Body Constitution ,Female ,Insulin Resistance ,business ,Body mass index ,Food Science - Abstract
Objective: We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity. Research Methods and Procedures: We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 ± 0.3%) and high (9.8 ± 1.5%) liver fat. The groups were almost identical with respect to age (36 ± 1 vs. 38 ± 1 years in low vs. high-LFAT), body mass index (32.2 ± 0.6 vs. 32.8 ± 0.5 kg/m2), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. Results: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 ± 0.21 vs. 1.11 ± 0.09 mM, p < 0.01) and insulin (14 ± 3 vs. 10 ± 1 mU/L, p < 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. Discussion: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.
- Published
- 2002
42. Application of Self-Organising Maps in Automated Chemical Shift Correction of In Vivo 1H MR Spectra
- Author
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Juhani Pulkkinen, Yrjö Hiltunen, Mika Lappalainen, Anna-Maija Häkkinen, Nina Lundbom, and Risto A. Kauppinen
- Subjects
Self-organizing map ,medicine.diagnostic_test ,Artificial neural network ,Computer science ,business.industry ,Chemical shift ,Magnetic resonance imaging ,Pattern recognition ,Nuclear magnetic resonance spectroscopy ,Mass spectrometry ,Spectral line ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Proton NMR ,Calibration ,Artificial intelligence ,Spectroscopy ,Spectral method ,business ,030217 neurology & neurosurgery - Abstract
Frequency shift differences in 1H MRSI spectra due to magnetic field inhomogeneities pose a problem, if automated lineshape fitting routines (LF) or artificial neural network (ANN) methods are used for spectral quantification. Use of self-organizing map (SOM) analysis for automated shift correction of long echo time (TE=270 ms) in vivo 1H NMR spectra of human brain is demonstrated. The map is obtained by training a SOM with proton spectra and the chemical shifts of the reference vectors were calibrated. The maps were then used for classification of spectroscopic imaging data and the calibration information for corrections of chemical shifts.
- Published
- 2002
43. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle
- Author
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Takashi Goto, Anna-Maija Häkkinen, Anneli Seppälä-Lindroos, Hannele Yki-Järvinen, Juha Halavaara, Satu Vehkavaara, Elena Korsheninnikova, and Antti Virkamäki
- Subjects
Adult ,Male ,medicine.medical_specialty ,Vastus lateralis muscle ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,medicine.medical_treatment ,Lipolysis ,Phosphatidylinositol 3-Kinases ,Insulin resistance ,Internal medicine ,Internal Medicine ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,Phosphorylation ,biology ,Skeletal muscle ,Glucose clamp technique ,medicine.disease ,Lipid Metabolism ,Receptor, Insulin ,Insulin receptor ,Endocrinology ,medicine.anatomical_structure ,Glucose ,biology.protein ,Glucose Clamp Technique ,Tyrosine ,Insulin Resistance ,Signal Transduction - Abstract
To examine whether and how intramyocellular lipid (IMCL) content contributes to interindividual variation in insulin action, we studied 20 healthy men with no family history of type 2 diabetes. IMCL was measured as the resonance of intramyocellular CH(2) protons in lipids/resonance of CH(3) protons of total creatine (IMCL/Cr(T)), using proton magnetic resonance spectroscopy in vastus lateralis muscle. Whole-body insulin sensitivity was measured using a 120-min euglycemic-hyperinsulinemic (insulin infusion rate 40 mU/m(2). min) clamp. Muscle biopsies of the vastus lateralis muscle were taken before and 30 min after initiation of the insulin infusion to assess insulin signaling. The subjects were divided into groups with high IMCL (HiIMCL; 9.5 +/- 0.9 IMCL/Cr(T), n = 10) and low IMCL (LoIMCL; 3.0 +/- 0.5 IMCL/Cr(T), n = 10), the cut point being median IMCL (6.1 IMCL/Cr(T)). The groups were comparable with respect to age (43 +/- 3 vs. 40 +/- 3 years, NS, HiIMCL versus LoIMCL), BMI (26 +/- 1 vs. 26 +/- 1 kg/m(2), NS), and maximal oxygen consumption (33 +/- 2 vs. 36 +/- 3 ml. kg(-1). min(-1), NS). Whole-body insulin-stimulated glucose uptake was lower in the HiIMCL group (3.0 +/- 0.4 mg. kg(-1). min(-1)) than the LoIMCL group (5.1 +/- 0.5 mg. kg(-1). min(-1), P < 0.05). Serum free fatty acid concentrations were comparable basally, but during hyperinsulinemia, they were 35% higher in the HiIMCL group than the LoIMCL group (P < 0.01). Study of insulin signaling indicated that insulin-induced tyrosine phosphorylation of the insulin receptor (IR) was blunted in HiIMCL compared with LoIMCL (57 vs. 142% above basal, P < 0.05), while protein expression of the IR was unaltered. IR substrate-1-associated phosphatidylinositol (PI) 3-kinase activation by insulin was also lower in the HiIMCL group than in the LoIMCL group (49 +/- 23 vs. 84 +/- 27% above basal, P < 0.05 between HiIMCL and LoIMCL). In conclusion, IMCL accumulation is associated with whole-body insulin resistance and with defective insulin signaling in skeletal muscle independent of body weight and physical fitness.
- Published
- 2001
44. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients
- Author
-
Satu Vehkavaara, Anna-Maija Häkkinen, Takashi Goto, Juha Halavaara, Hannele Yki-Järvinen, Jukka Westerbacka, and Leena Ryysy
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Injections, Subcutaneous ,030209 endocrinology & metabolism ,NPH insulin ,Type 2 diabetes ,Carbohydrate metabolism ,Fatty Acids, Nonesterified ,Absorption ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Pancreatic hormone ,030304 developmental biology ,0303 health sciences ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Metformin ,Endocrinology ,Glucose ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Liver ,Injections, Intravenous ,Regular insulin ,Female ,business ,medicine.drug - Abstract
To determine causes of interindividual variation in insulin requirements, we recruited 20 type 2 diabetic patients with stable glucose control and insulin doses for >1 year on combination therapy with bedtime NPH insulin and metformin. Insulin absorption (increase in free and total insulin over 8 h after a subcutaneous dose of regular insulin) and actions of intravenous (6-h 0.3 mU x kg(-1) x min(-1) euglycemic insulin clamp combined with [3-3H]glucose) and subcutaneous (glucose infusion rate required to maintain isoglycemia and suppression of free fatty acids [FFAs]) insulin, liver fat content (proton spectroscopy), visceral fat (magnetic resonance imaging), weight, and body composition were determined. We found the following variation in parameters: insulin dose range 10-176 U (mean 42 U, fold variation 17.6x) or 0.13-1.39 U/kg (0.44 U/kg, 10.7x), absorbed insulin 10.6x, action of subcutaneous insulin to suppress FFAs 7.5 x and to stimulate glucose metabolism (M value) 11.5x, body weight 67-127 kg (91 kg, 1.9x), liver fat 2-28% (12%, 14x), and visceral fat 179-2,053 ml (1,114 ml, 11.5x). The amount of insulin absorbed, measured as either free or total insulin, was significantly correlated with its ability to suppress FFAs and stimulate glucose metabolism but not with the insulin dose per se. The actions of absorbed insulin were, on the other hand, significantly correlated with the daily insulin dose (r = 0.70 for action on FFAs, P < 0.001, and r = -0.61 for M value, P < 0.005). Actions of subcutaneous and intravenous insulin to suppress FFAs were significantly correlated (r = 0.82, P < 0.001, R2 = 67%). Of the measures of adiposity, the percent hepatic fat was the parameter best correlated with the daily insulin dose (r = 0.76, P < 0.001). The percent hepatic fat was also significantly correlated with the ability of intravenous insulin to suppress endogenous glucose production (r = 0.72, P < 0.005). We conclude that the major reason for interindividual variation in insulin requirements in type 2 diabetes is the variation in insulin action. Variation in hepatic fat content may influence insulin requirements via an effect on the sensitivity of endogenous glucose production to insulin.
- Published
- 2000
45. A reciprocal translocation between autosomes 8 and 10 in a boar used for artificial insemination service and its effects on litter size
- Author
-
Magnus Andersson, Seppo Kuosmanen, Auli Mäkinen, and Anna Maija Häkkinen
- Subjects
Litter (animal) ,Male ,BOAR ,Litter Size ,Offspring ,Swine ,medicine.medical_treatment ,Chromosomal translocation ,Biology ,Insemination ,Translocation, Genetic ,03 medical and health sciences ,Endocrinology ,Animal science ,Food Animals ,medicine ,Animals ,Insemination, Artificial ,030304 developmental biology ,Genetics ,0303 health sciences ,Autosome ,Artificial insemination ,030305 genetics & heredity ,General Medicine ,Breed ,Chromosome Banding ,Karyotyping ,Animal Science and Zoology ,Female - Abstract
The low number of piglets per litter was the reason why a Finnish Yorkshire breed boar used for artificial insemination (AI) was taken for cytogenetic study. The boar had a reciprocal translocation between autosomes 8 and 10, resulting in a reduction in its litter size of about 19%. In addition the litter sizes were counted from 16 female offspring of this 2n = 38,XY; rcp(8;10)(p1.1;q1.3) boar.
- Published
- 1999
46. On- and off-resonance spin-lock MR imaging of normal human brain at 0.1 T: possibilities to modify image contrast
- Author
-
Hannu J. Aronen, Anna-Maija Häkkinen, Antti T. Markkola, Jukka I. Tanttu, Juha Halavaara, and Usama Abo Ramadan
- Subjects
Adult ,Male ,Time Factors ,media_common.quotation_subject ,Biomedical Engineering ,Biophysics ,Field strength ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Reference Values ,medicine ,Contrast (vision) ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,media_common ,Analysis of Variance ,Pulse (signal processing) ,Chemistry ,Relaxation (NMR) ,Brain ,Human brain ,Middle Aged ,Image Enhancement ,Mr imaging ,Magnetic Resonance Imaging ,Amplitude ,medicine.anatomical_structure ,Female ,Spin lock ,030217 neurology & neurosurgery - Abstract
The aim of the present investigation was to determine spin lock (SL) relaxation parameters for the normal brain tissues and thus, to provide basis for optimizing the imaging contrast at 0.1 T. 68 healthy volunteers were included. On-resonance spin lock relaxation time (T1rho) and off-resonance spin lock relaxation parameters (T1rho(off), Me/Mo), MT parameters (T1sat, Ms/Mo), and T1, T2 were determined for the cortical gray matter, and for the frontal and parietal white matters. The T1rho for the frontal and parietal white matters ranged from 110 to 133 ms and from 122 to 155 ms with locking field strengths from 50 microT to 250 microT, respectively. Accordingly, the values for the gray matter ranged from 127 to 155 ms. With a locking field strength of 50 microT, T1rho(off) for the frontal and parietal white matters were from 114 to 217 ms and from 126 to 219 ms, and for the gray matter from 136 to 267 ms with the angle between the effective magnetic field (B(eff)) and the z-axis (theta) ranging from 60 degrees to 15 degrees, respectively. The T1rho of the white and gray matters increased significantly with increasing locking field amplitude (p0.001). The T1rho(off) decreased significantly with increasing theta (p0.001). T1rho and T1rho(off) with thetaor = 30 degrees were statistically significantly shorter in the frontal than in the parietal white matters (p0.05). The duration, amplitude and theta of the locking pulse provide additional parameters to optimize contrast in brain SL imaging.
- Published
- 1998
47. Multiphase segmented k-space velocity mapping in pulsatile flow waveforms
- Author
-
Riku Kivisaari, Veli-Pekka Poutanen, P. Hekali, Carl-Gustaf Standertskjöld-Nordenstam, Sauli Savolainen, and Anna-Maija Häkkinen
- Subjects
Image quality ,Biomedical Engineering ,Biophysics ,Pulsatile flow ,Sensitivity and Specificity ,Flow measurement ,Edge detection ,Imaging phantom ,Optics ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Physics ,business.industry ,Phantoms, Imaging ,Models, Cardiovascular ,k-space ,Image Enhancement ,Magnetic Resonance Imaging ,Flow (mathematics) ,Pulsatile Flow ,Spatial frequency ,business ,Artifacts ,Pulmonary Ventilation ,Blood Flow Velocity ,Biomedical engineering - Abstract
The aim of the present study was to obtain the precision of flow measurement in breath-hold segmented k-space flow sequences. The results are based on studies of pulsatile flow in a phantom tube. The ultimate purpose is to use these sequences to measure coronary flow. In abdominal and cardiothoracic magnetic resonance imaging the image quality is degraded due to respiratory motion. In the segmented k-space acquisition method, one obtains many phase-encoding steps or views per cardiac phase. This shortens imaging time in the order of phase-encoding lines and makes it possible to image in a single breath-hold, thereby eliminating respiratory artefacts and improving edge detection. With breath-hold multiframe cine flow images it is possible to evaluate flow in all abdominal and cardiothoracic areas, including the coronary arteries. Our study shows that velocity curves shift in time when the number of k-space ky-lines per segment (LPS) are varied; this shift is linear as a function of LPS. The mean velocity Vmean in the center of mass of the pulsatile peak is constant (Vmean = 40.1 ± 2.9 cm/s) and time t = −10.1 × LPS + 268 (r = 0.993, p < 0.0001). Correlation between theoretical and experimental flow curves is also linear as a function of LPS: C = −0.977 ∗ LPS (r = 0.987, p < 0.0001). It is concluded that velocity curves move with LPS and are smoothed when the breath-hold velocity mapping is used. The more LPS is gathered the more inaccurate results are. LPS 7 or more cannot be considered clinically relevant.
- Published
- 1998
48. Simultaneous use of Gd-DTPA and spin-lock imaging: a Phantom Study
- Author
-
Usama Abo Ramadan, Anna-Maija Häkkinen, Hannu J. Aronen, Antti T. Markkola, Sauli Savolainen, and Jukka I. Tanttu
- Subjects
Gadolinium DTPA ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Materials science ,Phantoms, Imaging ,Contrast Media ,Radiology, Nuclear Medicine and imaging ,Spin lock ,Magnetic Resonance Imaging ,030217 neurology & neurosurgery ,Imaging phantom ,030218 nuclear medicine & medical imaging - Published
- 1998
49. Improvement of brain lesion detection at 0.1 T by simultaneous use of Gd-DTPA and magnetization transfer imaging
- Author
-
Kalevi Kairemo, Hannu J. Aronen, Pertti T. Karjalainen, Usama Abo Ramadan, Anna-Maija Häkkinen, Juha E. Jääskeläinen, Jukka I. Tanttu, and Leena M. Sipilä
- Subjects
Adult ,Gadolinium DTPA ,Male ,Contrast enhancement ,Hot Temperature ,Contrast Media ,Gadolinium ,Paramagnetic Contrast Agent ,Imaging phantom ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Organometallic Compounds ,Medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Magnetization transfer imaging ,Computer Simulation ,Magnetization transfer ,Bovine serum albumin ,Aged ,biology ,business.industry ,Brain Neoplasms ,Phantoms, Imaging ,Brain ,Serum Albumin, Bovine ,Glioma ,Middle Aged ,Pentetic Acid ,Image Enhancement ,Magnetic Resonance Imaging ,3. Good health ,Contrast medium ,cardiovascular system ,biology.protein ,Brain lesions ,Cattle ,Female ,business ,Nuclear medicine ,Artifacts ,Meningioma ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
Imaging parameters were optimized at 0.1 T to improve contrast-to-noise ratios (CNR) when combining magnetization transfer (MT) imaging and the use of paramagnetic contrast medium. This was accomplished by imaging a phantom containing serial concentrations of Gd-DTPA in cross-linked bovine serum albumin. With the use of simulations, the dependence of CNR on imaging parameters was studied. Conventional and MT images were obtained from 10 brain tumor patients with single and triple doses of Gd-DTPA. Simulations demonstrated the importance of TR in postcontrast sequences. The CNR in MT images is less sensitive to TR than in conventional images. A significant CNR improvement caused by MT remains at longer TR when there is no contrast enhancement without MT. The clinical results indicate that a single dose of Gd-DTPA combined with MT cannot replace imaging with a triple dose. However, MT significantly improved the CNR after single and triple Gd-DTPA-doses on T1-weighted and proton-density images.
- Published
- 1997
50. W12.303 Liver fat is a determinant of postprandial lipemia
- Author
-
J. Vakkilainen, M.-R. Taskinen, S. Mänttäri, Aino Soro-Paavonen, and Anna-Maija Häkkinen
- Subjects
medicine.medical_specialty ,Endocrinology ,Postprandial ,business.industry ,Internal medicine ,Liver fat ,Internal Medicine ,Medicine ,General Medicine ,Cardiology and Cardiovascular Medicine ,business ,A determinant - Published
- 2004
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