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SPECT
Tc99m-HMPAO BRAIN UPTAKE IN NORMAL Article Nº
AJ01-3 |
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| ABSTRACT We report on SPECT Tc99m-HMPAO (HMPAO) brain uptake of normal children, and compare it to results in elderly normal individuals. The pediatric HMPAO results are critical for the analysis of psychiatric and neurologic disorders in children. METHODS: The HMPAO normal subjects include: 13 children, 8 males and 5 females, 6 to 15 years (yr.) of age, mean 9.3 yr. with standard deviation of 3.2 yr. (SD),(table 1) and 20 elderly, 11 males and 9 females, mean 65.1 (9) yr. HMPAO was given intravenously in a dose of 0.3mCi/Kg in children and 30 mCi in adults. Imaging was performed in adults with a 3 ring brain dedicated imaging device (Shimadzu, Headtome, Kyoto, Japan) and in children with a rectangular single head digital SPECT camera (Elscint, Haifa, Israel). Six 1.6cm thick contiguous transaxial slices were analyzed by automated cortical gray-matter edge detection technique defining 12 regions of interest (ROI) per slice. RESULTS: The HMPAO data was normalized in children and adults to the maximal brain activity and also to the maximal activity in the cerebellum, the results expressed as mean percentage uptake of each ROI. Homogeneous distribution of HMPAO uptake was observed throughout the cerebral cortex. A MANOVA analysis demonstrates age related decreasing HMPAO uptake distribution in both parietal-occipital and frontal lobe regions. CONCLUSIONS: We report new reference values of normal HMPAO cerebral uptake in children ages 6 to 15 years. We also demonstrate normal age related changes in HMPAO brain uptake. Key Words: Children; Normal Results; HMPAO; SPECT RESUMEN Este trabajo comunica los resultados de captación de Tc-99m (HMPAO) en niños normales determinado mediante NeuroSPECT, Se comparan además estos resultados con la distribución de HMPAO en individuos normales mayores de 50 años. Resultados de distribución normal de HMPAO en el cerebro son críticos para el análisis de alteraciones neurológicas y psiquiátricas en niños. METODO: Los individuos normales estudiados con HMPAO incluyen: 13 niños, 8 varones y 5 mujeres de 6 a 15 años de edad, promedio 9.3 años con desviación standard de 3.2 años (D S) (Tabla 1) Se comparan además con 20 individuos normales, 11 varones y 9 mujeres promedio 65.5. años (9) HMPAO se administró por vía endovenosa en una dosis de 0.3 mCi/Kg en niños y 30mCi/Kg en adultos. Imágenes se obtuvieron en los adultos con un sistema dedicado de 3 anillos (Shimatzu, Heradtome, Kyoto, Japón) y en niños con una cámara de cabeza rectangular digital Spect (Elscint, Haifa, Israel). Se obtuvo seis cortes contiguos transaxiales de 1.6 cm. de grosor y se analizaron con un sistema automático de detección del borde externo de la sustancias gris y definiendo 12 regiones de interés en cada corte. RESULTADOS: La data de HMPAO fue normalizada en niños y en adultos a la máxima actividad en el cerebro y en los niños además a la máxima actividad en el cerebelo. Los resultados son expresados como porcentaje promedio de captación en cada región de interés. Se observó una distribución homogénea de HMPAO a través de toda la corteza cerebral. Un análisis de MANOVA demuestra disminución de la captación de HMPAO en ambos lóbulos parietales y occipitales y regiones frontales en función de la edad significando una disminución del flujo cerebral regional. CONCLUSIONES: Comunicamos resultados de captación normal de HMPAO en niños de edades 6 a 15 años. Demostramos además cambios en la distribución de HMPAO en el cerebro en función de la edad. Palabras Claves: Pediatria,SPECT, rCBF Normal,HMPAO.
INTRODUCTION Normal control values of SPECT Tc99m-HMPAO brain uptake is critical for accurate analysis of psychiatric and neurologic disorders in children. It is recognized that the distribution of cerebral perfusion significantly changes from the time of birth to about the age of 2 to 5 years. This is related to the normal cerebral maturation process demonstrated previously utilizing SPECT Xe133, F123IMP, and PET FDG imaging (1-8). After the age of two to five years several investigators have found that the overall cerebral perfusion normally diminishes with advancing age. (9-12). To the authors' knowledge, the only previously published information regarding normal HMPAO brain uptake in children is limited to a retrospective analysis of data of symptomatic pediatric patients with suspected risk factors for neurological disorder who were evaluated with an HMPAO examination and had subsequently an unremarkable clinical evolution, and were therefore considered normal (13). We report on results of prospectively acquired normal pediatric HMPAO brain uptake studies of asymptomatic, neuropsychologically intact subjects. We also compare the pediatric HMPAO results with elderly normal individuals.
MATERIALS AND METHODS The protocols for the pediatric HMPAO data acquisition performed in Chile , were approved by the local ethical committee and written informed consent was obtained. IRB at Harbor-UCLA specifically granted permission for the Chilean pediatric studies to be analyzed at Harbor-UCLA. SUBJECTS:
The procedure for the selection of the normal pediatric subjects was as follows: the children were selected from two sources: a) those attending elective non cranial surgery at a public hospital and b) volunteer health personnel relatives. Neuropsychiatric screening included: a) semistructured interview of the mother and child, b) mental status and neurologic examination performed by two child psychiatrists. Exclusion criteria included the following: positive pre, peri or post natal history, developmental disorder or delay of any kind, learning disorder, psychiatric disorder or isolated emotional or behavioral symptoms, severe family psychopathology or neurologic disorder, abnormal neurologic examination, and school underachievement. Using these criteria more than 50% of potential subjects were rejected. The other HMPAO normal subjects include: 20 elderly, 11 males and 9 females, mean age of 65.1 yr., + 9 yr. These subjects were determined normal by similar criteria as the children subjects. In addition, all subjects of the elderly group had a normal brain MRI examination. This data was gathered at Harbor-UCLA Medical Center, in Torrance California. Imaging Protocol: The subjects laid in supine position, with the head fastened and positioned carefully in order to obtain an optimal orbito-meatal line angle and a vertical midline. The alignment technique assures that the parallel transaxial cuts are along the orbito-meatal line and possible lateral tilting of the head is also corrected. Environmental stimuli such as light and noise were controlled, particularly at the time of HMPAO intravenous injection. The patient's antecubital vein is cannulated and 10 minutes later a HMPAO dose of 0.3mCi/kg for children and a dose of 30 mCi (1 100 MBq) for adults was administered intravenously. All subjects were maintained in a low ambient light and noise environment during the intravenous injection and brain uptake phase (2 minutes after injection). No child required sedation. One hour after injection, imaging of HMPAO distribution in the cerebral cortex in adults is performed utilizing a high sensitivity brain dedicated system that provides high count-rate dynamic studies and uses a fan beam high resolution collimator (Headtome 2 SET 031, Shimadzu, Kyoto, Japan). In children, imaging was performed with a rectangular single head, rotating SPECT camera (Elscint). 3D images of the brain were analyzed by means of 12 contiguous transaxial, coronal and sagittal cuts. Data analysis: All HMPAO studies had the same post acquisition image processing which was performed at Harbor-UCLA Medical Center. Image reconstruction was done with the backprojection reconstruction algorithm using the Butterworth and Ramachandran filters. An automated cortical gray-matter edge detection technique defined 12 regions of interest (ROI) per slice. The pediatric HMPAO data was normalized to the maximal brain activity and also to maximal cerebellar activity; In the adult the results were expressed as mean percentage uptake of each ROI. We applied Chang's attenuation correction which achieves a spatial resolution of 8 mm in the brain cortex, and 9.6 mm at the level of the basal ganglia in the elderly studies and 14mm in the cortex in the brain cortex. Twelve contiguous transaxial images were displayed with a color scale based on regional tracer uptake that defines the normal to abnormal cortical interfaces at 60 % of maximal activity in the brain with a 95 % confidence level (14). Statistical analysis of the data consists of a MANOVA analysis of the two different age group, comparing corresponding ROI values.
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| RESULTS Normal Children HMPAO Brain Uptake . There is homogeneous HMPAO uptake throughout both hemispheres, in all cortical regions, except for the inferior most slice and the bilateral inferior frontal lobe and anterior temporal lobe ROls. Furthermore, the variability of the results is low as demonstrated by the homogeneously low standard deviation values of each ROI. The distribution of HMPAO brain uptake in
normal children is shown in Figure 2. Each ROI's mean percentage (%) of maximal
brain cortical uptake and its standard deviation are reported for six adjacent transaxial
slices, with 12 ROIs per slice. Figure 3 demonstrates the same normal pediatric
data, reporting each ROI as the % uptake of maximal cerebellar activity. |
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Figure 2 (zoom = click) |
Figure 3 (zoom =click) |
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Normal Results of HMPAO Brain Uptake in Elderly Adults: Figure 4 depicts the ROI values of HMPAO brain uptake in elderly normal adult subjects . Age Comparison between Groups: A MANOVA statistical analysis comparing
the brain HMPAO uptake between the two different age groups (Figure 5) demonstrates
significant age related decrease of HMPAO uptake distributed in both parietal-occipital
and frontal lobe regions, (p<0.05 and p<0.001), |
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Figure 4 (zoom = click) |
Figure 5 (zoom = click) |
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DISCUSSION We report on results of Tc99m-HMPAO SPECT brain cortical uptake in normal children.. There is limited data presently available in the medical literature of retrospective analysis of data acquired on asymptomatic, hospitalized patients who were evaluated with HMPAO and subsequently were presumed normal (6, 1 l). The normal subjects in our project were all asymptomatic, not hospitalized, and neuro-psychiatrically normal. The normal HMPAO brain uptake data is essential for the accurate evaluation of pediatric neurological and psychiatric disorders such as attention deficit disorders, seizure disorder, trauma, near-drowning, chronic fatigue (15) among many others. lt. is important to note that our research protocol met all the requirements of the local participating hospital ethical committees. The parents' educational level was mainly high school level and the fathers' occupational level was predominantly skilled manual labor. All children's parents fully understood the implications of this noninvasive procedure and how these results would be utilized, and consented to the study in writing. All received a report of the results. The age group that our pediatric HMPAO normal brain uptake results is applicable is only for children ages 5 to 15 years, and not younger. It has been previously demonstrated that between the time of birth and 2 to 3 years of age, there is significant, progressively increasing, cerebral perfusion which is thought to be related to the rapid brain maturation process occurring during this time. Chiron et al. (1992) demonstrated with their normal children SPECT Xel33 brain rCBF data, that after the age of 2 to 3 years, there appears to be a leveling off of the cerebral perfusion of children which reaches stable pick levels between the approximate ages of 3 to 10 years, and then is followed by a small gradual decrease in cerebral perfusion to reach young adult levels by about 15 to 20 years of age. To the authors' knowledge, the only normal data base available for evaluation of cerebral perfusion with SPECT HMPAO brain uptake in neonates, infants and young children of ages up to 2 to 3 years, was published by Denays et al. (1992), who analyzed HMPAO data gathered on hospitalized patients, including this age group, who were assumed subsequently to be normal. It is difficult to compare our results with that of this last group's work since different data analysis methods were utilized. Although other investigators have found no significant normal age related decrease in cerebral cortical HMPAO uptake after the age of 15 years (1 l), we found a statistically significant progressive decrease in uptake among our two different age groups normal populations. The fact that these apparently normal age-related changes do occur makes it imperative to compare all brain HMPAO uptake examinations to an appropriate age control population. The normal pediatric HMPAO ROI uptake values were analyzed and reported in two different manners: % uptake of the maximal cortical activity and % uptake of the maximal cerebellar activity. These two different types of analysis were performed so as to make our data more useful for possible comparison of our data with other investigator's data utilizing different normalization techniques. The HMPAO normal cerebral uptake data did not evaluate any subcortical brain region. lt. is important to recognize that a decreased HMPAO brain uptake is seen in the most inferior ROIS, namely in the anterior temporal and frontal lobe regions. This finding may be due to a partial volume effect in the most peripheral anterior, inferior brain convexity regions related to misrepresented ROI placement by automated cortical gray-matter edge detection technique utilized. On the other hand, these lower HMPAO uptake areas may represent a real finding of diminished uptake in these areas. The answer to this question will become more evident when a greater number of normal cases are analyzed. Yet, since the SPECT acquisition and automated data analysis are always performed in the same manner, all future patient HMPAO examinations will be compared to these normal results which will already have these lower bilateral anterior inferior frontal lobe and anterior temporal lobe ROIs values. CONCLUSIONS We report new reference values of normal HMPAO cerebral uptake in children ages 6 to 15 years. This is an important control resource for accurately interpreting brain SPECT HMPAO examinations in children. Furthermore, we have found that normal brain HMPAO uptake diminishes as a function of age starting from mid-childhood and continuing throughout adult life. This finding correlates well with results of normal Xe-133 rCBF data which depicts a diminishing cerebral perfusion from childhood to late adulthood. (4). REFERENCES
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