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.

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.

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.

Cerebral metabolic rate for glucose during the first six months of life: an FDG positron emission tomography study.

AIM: To measure the local cerebral metabolic rate for glucose (LCMRGlc) in neonatal brains during maturation using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). METHODS: Twenty infants were studied using PET during the neonatal period. The postconceptional age ranged from 32.7 to 60.3 weeks. All infants had normal neurodevelopment and were normoglycaemic. The development of the infants was carefully evaluated (follow up 12-36 months) clinically, and by using a method based on Gesell Amatruda's developmental diagnosis. LCMRGlc was quantitated using PET derived from FDG kinetics and calculated in the whole brain and for regional brain structures. RESULTS: LCMRGlc for various cortical brain regions and the basal ganglia was low at birth (from 4 to 16 mumol/100 g/minute). In infants 2 months of age and younger LCMRGlc was highest in the sensorimotor cortex, thalamus, and brain stem. By 5 months, LCMRGlc had increased in the frontal, parietal, temporal, occipital and cerebellar cortical regions. In general, the whole brain LCMRGlc correlated with postconceptional age (r = 0.90; P < 0.001). The change in the glucose metabolic pattern observed in the neonatal brain reflects the functional maturation of these brain regions. CONCLUSION: These findings show that LCMRGlc in infants increases with maturation. Accordingly, when LCMRGlc is measured during infancy, the postconceptional age has to be taken into account when interpretating the results.

Estimated radiation dose to the newborn in FDG-PET studies.

UNLABELLED: The aim of this study was to estimate the radiation dose due to intravenous injection of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for infants studied with PET. METHODS: The radioactivity concentration in the brain and bladder content was measured with PET to determine the cumulated activity in these organs in 21 infant FDG studies. The individual organ masses were estimated according to the whole-body and brain masses, and they were used to calculate the absorbed dose per unit cumulated activity (S values). For organs other than brain and bladder, the cumulated activity was defined from adult studies. For each individual patient, the absorbed dose to the brain, bladder wall and selected organs were calculated. An estimation of the effective dose was determined. RESULTS: Whole-body distribution of FDG in the infants differed from adults: a greater proportion of the injected activity accumulated into the brain (9% versus 7%) and less was excreted to urine (7% versus 20% respectively). The measured cumulated activity in the brain was 0.25 MBq.h/MBq and in the bladder content 0.04 MBq.h/MBq with a large individual variation in latter. The calculated absorbed dose was 0.24 mGy/MBq to the brain and 1.03 mGy/MBq to the bladder wall. The estimated effective dose was 0.43 mSv/MBq. CONCLUSION: The dose to the bladder wall was lower in infants as compared to adults with ordinary amounts of injected activity. The greater amount of activity remaining in the body may increase the dose to other organs. The effective dose was lower compared to adults and conventional nuclear medicine studies of infants. PET can be a valuable tool in pediatric nuclear medicine because of good resolution images, sensitive radiation measurement and a variety of tracers labeled with short-lived isotopes.

FDG-PET in early infancy: simplified quantification methods to measure cerebral glucose utilization.

UNLABELLED: For further insight into the physiology and pathogenesis of the developing brain, quantification of the cerebral glucose metabolism is needed. Arterial blood sampling or sampling of great volumes of blood is not justified for the purpose of PET studies in children. Therefore, we have developed simplified PET approaches to analyze brain FDG examinations during infancy. METHODS: The study consisted of 18 FDG-PET examinations chosen from our research protocols concerning hypoxicischemic encephalopathy and severe neonatal hypoglycemia. The input function for graphical analysis according to Patlak was derived in two ways: (1) a combined time-activity curve derived from the left ventricular activity concentration (first 7-17 min of the study) and radioactivity concentration in venous whole-blood samples and; (2) activity concentration measured in whole-blood venous blood samples (arterial plasma in one case). As an alternative for semiquantitation, the standardized uptake values (SUV) were calculated and correlated to local cerebral metabolic rates for glucose (LCMRGlc). RESULTS: The influx rate constants (Ki) and LCMRGlc values obtained using the combined curve versus venous curve did not differ statistically (p > 0.05). There was a good correlation between the SUV and LCMRGlc values (r = 0.83, p < 0.001). CONCLUSION: Local cerebral metabolic rates for glucose can be accurately calculated by using the combined curve (left ventricular activity concentration during first 5 min of the study and 2-3 venous whole-blood samples at the end of the study) for even the smallest pediatric patients. When blood samples cannot be obtained, SUV values provide an alternative for estimation of the cerebral glucose uptake and interindividual comparison of the patients.

Meconium aspiration syndrome.

In the years 1977-82, 43 infants with the meconium aspiration syndrome (MAS) were managed at the Department of Paediatrics of Turku University Central Hospital (TUCH), Finland. Among 5,353 deliveries in one year the incidence of meconium staining was 8.7%. By extrapolation, the incidence of meconium aspiration in all newborns is approximately 0.13%. The mean duration of the pregnancies was 39.2 +/- 2.6 (SD) weeks and the weight of newborns was 3570 +/- 692 g which were similar to those of the reference group. The rate of Cesarean sections in the group with MAS was significantly higher than in the reference group (40% and 11.6%, respectively). Sixty-nine per cent of the newborns with MAS showed signs of depression during or after labour, while the incidence of same symptoms in the reference group was only 2.7% (P < 0.001). None of the infants with MAS died. Late sequelae were encountered in three babies in 1 to 6 years of follow-up.

Repeated fluorodeoxyglucose positron emission tomography of the brain in infants with suspected hypoxic-ischaemic brain injury.

Positron emission tomography (PET) permits the study of cerebral metabolism in vivo. We performed repeated PET studies with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for estimation of neurological prognosis in infants with suspected hypoxic-ischaemic brain injury. Fourteen infants (gestational age 35.3 +/- 4.67 weeks) were examined during the neonatal period (at age 38.4 +/- 2.7 weeks) and again at the age of 3.5 +/- 0.7 months; one further infant was studied only once at the age of 2.5 months. All children also underwent ultrasound examinations. Electroencephalography and computed tomography or magnetic resonance imaging were performed according to their clinical condition and their neurological development has been followed. FDG accumulated most actively in the subcortical areas (thalami, brainstem and cerebellum) and the sensorimotor cortex during the neonatal period. The repeated PET study showed that the uptake of FDG was markedly high and increased in all brain sections of infants with normal development (n = 11), whereas those with delayed development (n = 4) had significantly lower values (P < or = 0.005).

Examination of infant brain maturation using ultra low field MRI.

The brains of 42 newborn infants were examined with MRI at 0.02 T field, and regional variations of T1 relaxation time were measured from the images. There were three groups: 1. full term infants (9), 2. preterm infants (10) and 3. SGA (= small for gestational age) infants (20). Relaxation times showed a correlation to myelination of the brain. The brain of SGA infants showed a large variation in their T1 values.