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Biomedical subjects

U Ruotsalainen

Publications and source records attributed to U Ruotsalainen.

At least 19 recordsLinked to original sources

Cerebral glucose metabolism in survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Cranial radiation therapy (CRT) has been suggested to be a principal factor responsible for long term neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL). However, neither reduction of the irradiation dose nor the elimination of irradiation entirely appear to have abolished neurocognitive impairment in long term ALL survivors. Positron emission tomography (PET) and [(18)F]-fluorodeoxyglucose (FDG) can be used to quantitate cerebral glucose metabolism, a potential indicator of treatment-induced adverse central nervous system (CNS) effects. The purpose of this study was to assess whether CRT is associated with defects in cerebral glucose metabolism in long term ALL survivors. The authors also studied whether chemotherapy and/or the severity of disease have deleterious effects on glucose metabolism. METHODS: Forty long-term survivors of childhood ALL were studied using FDG PET. All subjects went through an elaborate neurocognitive assessment. In 20 of these children, the prophylactic treatment of the CNS had been CRT combined with methotrexate (MTX), and it was MTX only in the remaining 20 children. RESULTS: No major differences were found in the regional cerebral glucose utilization or in neurocognitive performance between the irradiated and nonirradiated groups. A high leukocyte count at the time of diagnosis was found to be associated inversely with cerebral glucose utilization. CONCLUSIONS: CRT does not appear to affect cerebral glucose metabolism in long term survivors of ALL. By contrast, the association between the leukocyte count and glucose utilization implies that disease severity may be partly responsible for adverse CNS effects in long term survivors of childhood ALL.

Adolescent↗

Extracting VOIs from brain PET images.

A semi-automatic system for determining volumes of interest (VOI) from positron emission tomography (PET) scans of brain is described. The VOIs surface extraction is based on user selectable threshold and three-dimensional target flood-fill. Contrast to anatomical volume detection approaches, volumes are determined from functional PET images and the obtained objects are checked against anatomical images. The developed VOI program was evaluated with brain FDOPA-PET studies where the striatum was the object. The results were comparable to entirely manual method and the target extraction time is reduced to about one third of manual method.

Algorithms↗

Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography.

In vitro studies have shown that insulin and exercise stimulate glucose uptake in part via distinct mechanisms. We determined whether a high rate of insulin-stimulated glucose uptake (good insulin sensitivity) is associated with an enhanced ability of exercise to increase glucose uptake in vivo in humans. In our study, 22 normal subjects performed one-legged isometric exercise for 105 min (45-150 min) under intravenously maintained euglycemic-hyperinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood flow, and glucose uptake were quantitated simultaneously in skeletal muscle of both legs using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one-legged exercise, performed at an intensity of 11% of maximal isometric force, was designed to induce similar increases in oxygen consumption in both groups. In the entire group, exercise increased oxygen consumption from 2.3 +/- 0.3 ml x kg(-1) muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1) muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose uptake was due to marked increases in blood flow (36 +/- 5 ml x kg(-1) muscle x min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x min(-1) [insulin and exercise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/- 0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/1 (insulin and exercise) (P < 0.001). The subjects were classified according to their mean rate of whole-body insulin-stimulated glucose uptake into those with high (49 +/- 3 micromol x kg(-1) x min(-1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1) muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x min(-1)) rates of oxygen consumption were comparable between the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 +/- 25 pmol x kg(-1) muscle x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol x kg(-1) muscle x min(-1)) (P < 0.05). Muscle blood flow was closely correlated with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin-stimulated (30 +/- 5 vs. 35 +/- 6 ml x kg(-1) muscle x min(-1)) and exercise-induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x min(-1)) in muscle blood flow were similar between the groups. Glucose extraction remained higher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05). We conclude that whereas acute exercise per se increases glucose uptake via increasing glucose delivery, good insulin sensitivity modulates exercise-induced increases in glucose uptake by enhancing cellular glucose extraction.

Adult↗

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Adult↗

Myocardial oxygen consumption is unchanged but efficiency is reduced in patients with essential hypertension and left ventricular hypertrophy.

BACKGROUND: Patients with hypertension and left ventricular hypertrophy (LVH) are prone to develop heart failure. We tested the hypothesis that compensatory LVH is associated with normalization of myocardial oxygen consumption and that this occurs at the expense of a decrease in the ratio between cardiac work and oxygen consumption (efficiency). METHODS AND RESULTS: Nine hypertensive men with LVH (LVH+) (age 42+/-2 years), left ventricular mass index (LVMI) 161+/-8 g/m(2), blood pressure (BP) 145+/-16/88+/-10 mm Hg (mean+/-SD); 8 hypertensive men without LVH (LVH-) (age 39+/-5 years, LVMI 107+/-15 g/m(2), BP 140+/-15/90+/-11 mm Hg); and 10 normotensive men (CONT) were studied. Myocardial blood flow, oxygen consumption, and glucose uptake were measured during euglycemic hyperinsulinemia using PET techniques. LV dimensions, volumes, and workload were determined by echocardiography, and efficiency was calculated. Myocardial workload (2.5+/-0.8 versus 3.0+/-0.6 versus 2. 3+/-0.5 mm Hg. mL. min(-1). g(-1) for CONT versus LVH- versus LVH+; P<0.05, LVH- versus LVH+), myocardial blood flow (0.84+/-0.16 versus 1.06+/-0.22 versus 0.81+/-0.09 mL. g(-1). min, respectively; P<0.05, LVH- versus other groups) and oxygen consumption (0.09+/-0.02 versus 0.14+/-0.03 versus 0.11+/-0.01 ml. g(-1). min(-1), respectively; P<0. 05, LVH- versus other groups) were increased in the LVH- group. Myocardial efficiency was reduced in the LVH+ group (18.1+/-4.1% versus 15.1+/-2.3% versus 13.5+/-1.9%, respectively; P<0.05, LVH+ versus CONT). CONCLUSIONS: Myocardial oxygen consumption per unit weight is increased in hypertensive patients without LVH but is normal in those with LVH. The normalization of oxygen consumption via hypertrophy occurs at the expense of efficiency, which may predispose hypertensive patients with LVH to heart failure.

Adult↗

Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia.

We have previously reported aberrations in the striatal presynaptic dopamine function in neuroleptic-naive schizophrenic patients compared to healthy controls (Hietala, J., Syvälahti, E., Vuorio, K. et al., 1995. Lancet 346, 1130-1131). In this extended study we explore whether the altered presynaptic dopamine function correlates with the clinical symptomatology in schizophrenia. Striatal dopamine synthesis capacity (6-[18F]fluorodopa (FDOPA) uptake, Ki values) was studied with positron emission tomography in 10 neuroleptic-naive schizophrenic patients and 13 healthy controls. The clinical symptomatology was characterized with the Positive and Negative Symptom Scale (PANSS). The patients had an increased FDOPA uptake in striatum and lacked the asymmetry in caudate FDOPA uptake (p = 0.0005), confirming our earlier results. Left striatal FDOPA uptake (Ki) values correlated negatively with depressive symptoms in a highly significant manner. On the other hand, paranoid symptomatology correlated positively with right putamen FDOPA uptake at a trend level (rho = 0.73, p < 0.02). The lack of asymmetry in caudate Ki values did not associate with any dimension of psychopathology. The major finding in this study is that depressive symptoms in neuroleptic-naive first-admission schizophrenia are associated with low presynaptic dopamine function. This link appears to be hemisphere-related and may have drug-treatment implications, e.g., in prediction of response to D2 receptor blocking antipsychotic drugs. A possible connection between paranoid symptomatology and subcortical hyperdopaminergia is suggested, but this remains to be further verified.

Adolescent↗

Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis.

Subacute and long-term stability of measurements of D2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [11C]-Raclopride and the transient equilibrium method were used to measure D2 receptor characteristics. The interval between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest analysis of quantitative measurements of D2 receptor Bmax and Kd was compared with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in the parameter estimation procedure was explored with simulations. The subacute test-retest indicates good reproducibility of D2 receptor density, affinity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements after 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute variability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulations indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good overall stability of the equilibrium method with [11C]raclopride for measuring dopamine D2 receptor binding characteristics in the striatum. The BP approach is more stable than Kd and especially Bmax measurements. Error in defining the tmax in particular in the low specific radioactivity scan may be one source of greater variability in Bmax versus BP. However, a higher intraindividual variability in measurements of the D2 receptor Bmax also may include a component of continuous regulation of this parameter over time. These methodologic aspects should be considered in the design and interpretation of longitudinal studies on D2 dopamine receptor characteristics with [11C]-raclopride.

Adult↗

[18F]FDG-PET and whole-scalp MEG localization of epileptogenic cortex.

PURPOSE: To evaluate combined [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 122-channel whole-scalp magnetoencephalography (MEG) in lateralizing the epileptogenic cortex in patients whose routine presurgical evaluations gave discordant results about the location of the epileptic focus. METHODS: Nine patients (five women, four men) aged 13-40 years were studied. Subdural EEG (SEEG) was recorded from eight patients. Six patients were operated on. RESULTS: In seven of nine patients, PET and MEG agreed in localizing the epileptogenic cortex. When PET and MEG were in congruence, SEEG agreed with the findings. In five of six operated-on patients, PET and MEG results were congruent, and the outcome of the operation was successful. Two patients had discordant PET and MEG results. In one patient, PET showed bitemporal hypometabolism, whereas MEG showed epileptiform activity in the right parietal lobe. The surgical outcome of the palliative temporal lobectomy was poor. Another patient had unilateral temporal hypometabolism in PET and bitemporal activity in MEG. She was not operated on. CONCLUSIONS: In most patients, PET and MEG were congruent in locating the epileptogenic cortex. Thus the combination of these techniques may provide useful support for the localization of the seizure onset and reduce the need for invasive procedures.

Adolescent↗

Myocardial blood flow, oxygen consumption, and fatty acid uptake in endurance athletes during insulin stimulation.

We have previously demonstrated reduced myocardial glucose uptake rates in hearts of endurance athletes, which could be due to increased use of alternative fuels or reduced energy demands. In the present study myocardial blood flow, oxygen consumption, and free fatty acid uptake were measured with [(15)O]H(2)O, [(15)O]O(2), [(18)F]FTHA, and positron emission tomography (PET) in 9 endurance athletes and 11 sedentary men during euglycemic hyperinsulinemia. Compared with sedentary men, athletes had 33% lower myocardial blood flow, 27% lower oxygen consumption, and 20% lower estimated myocardial work per gram of tissue. Myocardial fatty acid uptake rates were not significantly different in endurance athletes (0.83 +/- 0.29) and sedentary men (1.0 +/- 0.31 micromol. 100 g(-1). min(-1), P = 0.232). In conclusion, myocardial blood flow and oxygen consumption per unit mass of myocardium are reduced at rest in endurance athletes. This can be explained by reduced energy requirements per gram of tissue due to anatomic and physiological changes of the athlete's heart.

Adult↗

Iterative reconstruction based on median root prior in quantification of myocardial blood flow and oxygen metabolism.

UNLABELLED: The aim of this study was to compare reproducibility and accuracy of two reconstruction methods in quantification of myocardial blood flow and oxygen metabolism with 15O-labeled tracers and PET. A new iterative Bayesian reconstruction method based on median root prior (MRP) was compared with filtered backprojection (FBP) reconstruction method, which is traditionally used for image reconstruction in PET studies. METHODS: Regional myocardial blood flow (rMBF), oxygen extraction fraction (rOEF) and myocardial metabolic rate of oxygen consumption (rMMRO2) were quantified from images reconstructed in 27 subjects using both MRP and FBP methods. For each subject, regions of interest (ROIs) were drawn on the lateral, anterior and septal regions on four planes. To test reproducibility, the ROI drawing procedure was repeated. By using two sets of ROIs, variability was evaluated from images reconstructed with the MRP and the FBP methods. RESULTS: Correlation coefficients of mean values of rMBF, rOEF and rMMRO2 were significantly higher in the images reconstructed with the MRP reconstruction method compared with the images reconstructed with the FBP method (rMBF: MRP r = 0.896 versus FBP r = 0.737, P < 0.001; rOEF: 0.915 versus 0.855, P < 0.001; rMMRO2: 0.954 versus 0.885, P < 0.001). Coefficient of variation for each parameter was significantly lower in MRP images than in FBP images (rMBF: MRP 23.5% +/- 11.3% versus FBP 30.1% +/- 14.7%, P < 0.001; rOEF: 21.0% +/- 11.1% versus 32.1% +/- 19.8%, P < 0.001; rMMRO2: 23.1% +/- 13.2% versus 30.3% +/- 19.1%, P < 0.001). CONCLUSION: The MRP reconstruction method provides higher reproducibility and lower variability in the quantitative myocardial parameters when compared with the FBP method. This study shows that the new MRP reconstruction method improves accuracy and stability of clinical quantification of myocardial blood flow and oxygen metabolism with 15O and PET.

Adult↗

Three-dimensional ROIs in brain PET.

A semi-automatic system for determining volumes of interest (VOI) from positron emission tomography (PET) scans of brain is described. The VOIs surface extraction is based on user selectable threshold and three-dimensional target flood-fill. Contrast to anatomical volume detection approaches, volumes are determined from functional PET images and the obtained objects are checked against anatomical images. The developed VOI program was evaluated with brain FDOPA-PET studies where the striatum was the object. The results were comparable to entirely manual method and the target extraction time is reduced to about one third of manual method.

Algorithms↗

Increased brain glucose utilization in Salla disease (free sialic acid storage disorder).

UNLABELLED: Salla disease is an autosomal recessive lysosomal free sialic acid storage disorder characterized by psychomotor retardation and ataxia. MRI studies have revealed evidence of dysmyelination, but the biological mechanism of the brain dysfunction is unknown. METHODS: Nine patients with Salla disease (age 2.5 mo-42 y) presenting the disease in varying degrees of severity were studied by PET using 2-fluoro-2-deoxy-D-glucose (FDG) as a tracer. Local cerebral metabolic rates for glucose (LCMRGlc) in individual brain regions were compared with controls. RESULTS: The FDG PET results showed significantly increased LCMRGlc values in the frontal and sensorimotor cortex and especially in the basal ganglia of the patients. Cerebellar hypometabolism was present in all seven patients with marked ataxia, whereas the less severely affected patients without obvious ataxia had normal or even high glucose uptake in the cerebellum. CONCLUSION: The increased cerebral glucose utilization is a constant finding in Salla disease and may reflect the basic defect of the sialic acid metabolism in this disorder. The FDG PET findings in the cerebellum suggest a correlation between glucose uptake and the severity of the clinical symptoms.

Adolescent↗

Preserved relative dispersion but blunted stimulation of mean flow, absolute dispersion, and blood volume by insulin in skeletal muscle of patients with essential hypertension.

BACKGROUND: We examined the integrity of the effects of insulin on mean muscle blood flow, flow heterogeneity, and blood volume in essential hypertension. METHODS AND RESULTS: Positron emission tomography, combined with [15O]H2O and [15O]CO as tracers for direct measurement of blood flow and volume in skeletal muscle, and a new bayesian iterative reconstruction algorithm allowing pixel-by-pixel quantitation of blood flow and flow dispersion, were used. Measurements were performed basally after an overnight fast and under normoglycemic hyperinsulinemic conditions in 11 newly diagnosed, untreated mildly hypertensive men (age, 35 +/- 1 years; body mass index, 25.2 +/- 0.4 kg/m2, blood pressure 141 +/- 4/96 +/- 2 mm Hg, mean +/- SE) and 11 matched normotensive men. Insulin-stimulated whole body glucose uptake was significantly decreased in the hypertensive men (41 +/- 4 mumol/kg per minute) compared with the normotensive (59 +/- 4 mumol/kg per minute, P < 0.005) men. Mean blood flow in skeletal muscle was significantly lower in the hypertensive than the normal subjects basally (1.7 +/- 0.2 versus 2.7 +/- 0.4 mL/0.1 kg per minute, P < 0.05) and during hyperinsulinemia (2.3 +/- 0.2 versus 4.2 +/- 0.8, P < 0.05). The flow response to insulin (0.6 +/- 0.2 versus 1.9 +/- 0.5 mL/0.1 kg per minute, hypertensive versus normal subjects, P < 0.05) was also significantly blunted. Muscle blood volume was significantly lower in the hypertensive than in the normal subjects, both basally (3.0 +/- 0.2 versus 3.5 +/- 0.2 mL/0.1 kg, P < 0.05) and during hyperinsulinemia (3.1 +/- 0.2 versus 4.0 +/- 0.2 mL/0.1 kg muscle, P < 0.02). The increase in muscle blood volume by insulin was significant in the normal (P < 0.05) but not the hypertensive subjects. Regional pixel-by-pixel analysis within femoral muscles revealed significant spatial heterogeneity of blood flow. Insulin increased absolute dispersion of blood flow significantly more in the normal subjects than in the hypertensive subjects (P < 0.05). CONCLUSIONS: True flow heterogeneity, as judged from the coefficients of variation (relative dispersion), was comparable between the groups basally and during hyperinsulinemia. We conclude that mean flow, its absolute dispersion, and blood volume exhibit insulin resistance in patients with essential hypertension.

Adult↗

Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM.

Skeletal muscle insulin resistance and coronary heart disease (CHD) often precede non-insulin-dependent diabetes mellitus (NIDDM). A recent study showed the myocardium of patients with CHD to be insulin resistant, independent of blood flow. We determined whether myocardial insulin resistance is a feature of NIDDM patients with no CHD. Skeletal muscle and myocardial glucose uptake were determined in 10 patients with NIDDM and 9 age- and weight-matched normal men of similar age and body mass index men using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography under normoglycaemic hyperinsulinaemic conditions. Whole body glucose uptake, as determined by the euglycaemic clamp technique, was significantly lower in the patients with NIDDM (35+/-3 micromol/kg body weight min) than the normal subjects (45+/-3 micromol/kg body weight x min, p < 0.02). Insulin-stimulated femoral muscle glucose uptake was significantly lower in the patients with NIDDM (71+/-6 micromol/kg muscle x min) than in the normal subjects (96+/-5 micromol/kg muscle x min, p < 0.01). Whole body glucose uptake was correlated with femoral muscle glucose uptake in the entire group (r=0.76, p < 0.001), in patients with NIDDM and in normal subjects. Rates of insulin-stimulated myocardial glucose uptake were comparable between the patients with NIDDM (814+/-76 micromol/kg muscle min) and the normal subjects (731+/-63 micromol/kg muscle min, p > 0.4). Whole body or femoral muscle, and myocardial glucose uptake were not correlated in all subjects, patients with NIDDM or normal subjects. We conclude that insulin resistance of the myocardium is not a feature of uncomplicated NIDDM.

Blood Glucose↗

Insulin resistance in essential hypertension is characterized by impaired insulin stimulation of blood flow in skeletal muscle.

OBJECTIVE: To determine whether insulin-stimulated blood flow in patients with mild essential hypertension is altered. SUBJECTS: Eleven untreated mildly hypertensive patients [aged 35 +/- 2 years, body mass index 25.1 +/- 0.4 kg/m2, mean arterial pressure 110 +/- 2 mmHg (means +/- SEM) and 10 matched normotensive subjects (mean arterial pressure 94 +/- 3 mmHg). METHODS: Blood flow was quantitated directly in skeletal muscle both basally and during supraphysiologic hyperinsulinemia (serum insulin approximately = 450 mU/l) using radiowater ([15O]H2O) and positron emission tomography. Whole-body and femoral muscle glucose uptakes were determined using the euglycemic insulin clamp technique, [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography. RESULTS: Rates of whole-body and femoral muscle glucose uptake were significantly lower in the hypertensive than in the normotensive group. Insulin increased muscle blood flow by 91% in the normotensive group, but only by 33% in the hypertensive group. CONCLUSIONS: The ability of insulin to stimulate blood flow in patients with mild essential hypertension is impaired.

Adult↗

Intact insulin stimulation of skeletal muscle blood flow, its heterogeneity and redistribution, but not of glucose uptake in non-insulin-dependent diabetes mellitus.

We tested the hypothesis that defects in insulin stimulation of skeletal muscle blood flow, flow dispersion, and coupling between flow and glucose uptake contribute to insulin resistance of glucose uptake in non-insulin-dependent diabetes mellitus (NIDDM). We used positron emission tomography combined with [15O]H2O and [18F]-2-deoxy--glucose and a Bayesian iterative reconstruction algorithm to quantitate mean muscle blood flow, flow heterogeneity, and their relationship to glucose uptake under normoglycemic hyperinsulinemic conditions in 10 men with NIDDM (HbA1c 8.1+/-0.5%, age 43+/-2 yr, BMI 27.3+/-0.7 kg/m2) and in 7 matched normal men. In patients with NIDDM, rates of whole body (35+/-3 vs. 44+/-3 micromol/kg body weight.min, P < 0.05) and femoral muscle (71+/-6 vs. 96+/-7 micromol/kg muscle.min, P < 0.02) glucose uptake were significantly decreased. Insulin increased mean muscle blood flow similarly in both groups, from 1.9+/-0.3 to 2.8+/-0.4 ml/100 g muscle.min in the patients with NIDDM, P < 0.01, and from 2.3+/-0.3 to 3.0+/-0.3 ml/100 g muscle.min in the normal subjects, P < 0.02. Pixel-by-pixel analysis of flow images revealed marked spatial heterogeneity of blood flow. In both groups, insulin increased absolute but not relative dispersion of flow, and insulin-stimulated but not basal blood flow colocalized with glucose uptake. These data provide the first evidence for physiological flow heterogeneity in human skeletal muscle, and demonstrate that insulin increases absolute but not relative dispersion of flow. Furthermore, insulin redirects flow to areas where it stimulates glucose uptake. In patients with NIDDM, these novel actions of insulin are intact, implying that muscle insulin resistance can be attributed to impaired cellular glucose uptake.

Adult↗

Cerebral metabolic rate for glucose after neonatal hypoglycaemia.

OBJECTIVE: We studied the effect of neonatal hypoglycaemia on the local cerebral metabolic rate for glucose (LCMRglc). MATERIALS AND METHODS: Eight newborn infants with neonatal hypoglycaemia were studied. The LCMRglc in the whole brain, in five cerebral regions and in skeletal muscles were quantitated using positron emission tomography (PET) and 2-[18F]Fluoro-2-deoxy-D-glucose (FDG). The PET studies were performed at the age of 5.3 +/- 6.2 days during normoglycaemia. The LCMRglc of these infants were compared to the age-adjusted LCMRglc of eight infants with suspected hypoxic-ischaemic brain injury but with normal neurological development. RESULTS: After neonatal hypoglycaemia the age-adjusted LCMRglc in the whole brain was not lower than LCMRglc of the control infants (5.33 +/- 0.60 mumol/100 g/min vs. 6.71 +/- 0.60 mumol/100 g/min). Also the metabolic rate for glucose (MRglc) in the skeletal muscles was similar in hypoglycaemic and control infants (5.56 +/- 2.48 mumol/100 g/min vs. 6.99 +/- 2.41 mumol/100 g/min). CONCLUSION: MRglc in brain and in skeletal muscle seems to be normal after neonatal hypoglycaemia, although larger group of patients with more severe hypoglycaemia are needed to confirm this finding.

Animals↗

Bayesian image reconstruction for emission tomography based on median root prior.

The aim of the present study was to investigate a new type of Bayesian one-step late reconstruction method which utilizes a median root prior (MRP). The method favours images which have locally monotonous radioactivity concentrations. The new reconstruction algorithm was applied to ideal simulated data, phantom data and some patient examinations with PET. The same projection data were reconstructed with filtered back-projection (FBP) and maximum likelihood-expectation maximization (ML-EM) methods for comparison. The MRP method provided good-quality images with a similar resolution to the FBP method with a ramp filter, and at the same time the noise properties were as good as with Hann-filtered FBP images. The typical artefacts seen in FBP reconstructed images outside of the object were completely removed, as was the grainy noise inside the object. Quantitatively, the resulting average regional radioactivity concentrations in a large region of interest in images produced by the MRP method corresponded to the FBP and ML-EM results but at the pixel by pixel level the MRP method proved to be the most accurate of the tested methods. In contrast to other iterative reconstruction methods, e.g. ML-EM, the MRP method was not sensitive to the number of iterations nor to the adjustment of reconstruction parameters. Only the Bayesian parameter beta had to be set. The proposed MRP method is much more simple to calculate than the methods described previously, both with regard to the parameter settings and in terms of general use. The new MRP reconstruction method was shown to produce high-quality quantitative emission images with only one parameter setting in addition to the number of iterations.

Algorithms↗