Biomedical subjects

H T Chugani

Publications and source records attributed to H T Chugani.

At least 73 records · Page 4Linked to original sources

PubMed1997

Receptive and expressive language activations for sentences: a PET study.

Most language mapping studies have focussed on activations for single-word tasks. We examined activations for verbal auditory and generation tasks using sentence stimuli. [15O]-water PET was performed in 4 female and 5 male normal adults. Listening to sentences (minus rest) activated the superior and middle temporal gyri bilaterally, but mean activation was significantly stronger on the left. The strongest activation for sentence generation (minus repetition) was seen in the left middle and inferior frontal gyri (area 46). This focus appears to be anterior to activations reported for single-word generation, possibly due to greater verbal working memory demands of the sentential task. Additional activation of the left inferior temporal lobe can be attributed to lexicosemantic processing.

Acoustic Stimulation↗

PubMed1997

Plasticity of motor organization in children and adults.

We explored the effects of maturational plasticity on motor activations for the affected hand in patients with unilateral lesion involving the rolandic cortex. Ten patients with early lesion (onset < 4 years), seven patients with late lesion (onset > or = 10 years) and eight normal adults underwent [15O]-water positron emission tomography (PET). Rolandic activations in the contralesional hemisphere were enhanced in both patient groups when compared to normal adults. Secondary motor and frontoparietal nonmotor cortices were more activated in the early than in the late lesion group, suggesting a greater potential for reorganization during early development than later in life. Cerebellar activations were similar in late lesion patients and normal adults, but significantly weaker in early lesion patients.

Adolescent↗

PubMed1997

Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys.

Based on reports of increased platelet serotonin in 30 to 50% of autistic subjects, abnormal serotonergic neurotransmission may be important in the pathogenesis of autism. However, serotonin metabolite measurements in cerebrospinal fluid of autistic subjects have failed to demonstrate consistent abnormalities. Using alpha-[11C]methyl-L-tryptophan as a tracer for serotonin synthesis with positron emission tomography, we now report unilateral alterations of serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Asymmetries of serotonin synthesis were found in frontal cortex, thalamus, and dentate nucleus of the cerebellum in all 7 boys, but not in the 1 autistic girl studied. Decreased serotonin synthesis was found in the left frontal cortex and thalamus in 5 of the 7 boys and in the right frontal cortex and thalamus in the 2 remaining autistic boys. In all 7 cases, elevated serotonin synthesis in the contralateral dentate nucleus was observed. Statistically significant differences between autistic boys and their nonautistic siblings (n = 5) were obtained when comparing asymmetry indices for frontal cortex, thalamus, and dentate nucleus combined as well as individually for frontal cortex and thalamus. These serotonergic abnormalities in a brain pathway, important for language production and sensory integration, may represent one mechanism underlying the pathophysiology of autism.

Adolescent↗

PubMed1997

The value of positron emission tomography in the diagnosis and monitoring of late infantile and juvenile lipopigment storage disorders (so-called Batten or neuronal ceroid lipofuscinoses).

Positron Emission Tomography (PET) with 2-deoxy-2 [18F]-fluoro-D-glucose provides a measure of functional brain activity, particularly in the dendritic field. In CLN3 (juvenile neuronal ceroid lipofuscinosis or juvenile Batten disease, with fingerprint inclusions) hypometabolism slowly spreads from calcarine to anterior areas, sparing subcortical structures and brainstem. In CLN2 (late infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky disease, with curvilinear inclusions) degeneration is rapid with generalized cortical and subcortical hypometabolism. This is associated with rapidly progressive cerebral atrophy on anatomical neuroimaging. A 4-year-old child with CLN2 scanned with PET 13 months after the clinical onset showed hypometabolism, severe in the thalamus and mild in cortical areas. Three other patients with CLN2 had severe generalized hypometabolism and brain atrophy. Longitudinal PET studies in CLN may provide key insights into degenerative processes.

Blood Glucose↗

PubMed1997

Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo.

We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan (AMT), an analogue of tryptophan, which has been developed as a tracer for serotonin synthesis using positron emission tomography (PET) in human brain. Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series of 22 scans covering a total of 60 minutes and analyzed by means of a three-compartment, four-parameter model. In addition, functional images of the K-complex were created using the Patlak-plot approach. The application of a three-compartment model resulted in low identifiability of individual k-values, especially that of k3. Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identifiability to increase by 50% when the Patlak-plot approach was used. K-complex values derived by the Patlak-plot approach overestimated the compartmental values by 10 to 20%, because of the violation of the dynamic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < 0.0001). These results indicate that the Patlak-plot method can be readily applied to [C-11]AMT data in order to create functional images of the K-complex, reflecting serotonin synthesis rate, within an acceptable error margin.

Adult↗

PubMed1997

Identification of frontal lobe epileptic foci in children using positron emission tomography.

PURPOSE: Presurgical evaluation for intractable frontal lobe epilepsy (FLE) is difficult and invasive, partly because anatomic neuroimaging studies with computed tomography (CT) and magnetic resonance imaging (MRI) typically do not show a discrete lesion. In adult patients with FLE, functional neuroimaging of glucose metabolism with positron emission tomography (PET) is less sensitive in detecting focal metabolic abnormalities than in temporal lobe epilepsy (TLE). Comparable data on children with FLE are not available. METHODS: We used high-resolution PET scanning of glucose metabolism to evaluate 13 children (age 17 months to 17 years; mean age 9.5 years) with intractable FLE being considered for surgical treatment. Only children with normal CT and MRI scans were included. RESULTS: Hypometabolism including the frontal lobe was evident in 12 of the 13 children, was unilateral in 11 of 13, and was restricted to the frontal lobe in 8 of 13. One child showed bilateral frontal cortex hypometabolism and another had an ictal PET scan demonstrating unilateral frontal cortex hypermetabolism surrounded by hypometabolism. Additional hypometabolic areas outside the frontal cortex were observed in 5 children in parietal and/or temporal cortex. Localization of seizure onset on scalp EEG was available in 10 children and corresponded to the location of frontal lobe PET abnormality in 8. However, in 4 of the 10 children, the extent of hypometabolism exceeded the epileptogenic region indicated by ictal EEG. In 2 of the 13 children, the abnormality evident on EEG was more extensive than that evident on PET. In the remaining 3 children for whom only interictal EEG data were available, the PET foci did not correspond in location to the interictal EEG abnormalities. In 11 of the 13 children, the presumed region of seizure onset in the frontal lobe, as based on analysis of seizure semiology, corresponded to the locations of frontal lobe glucose metabolism abnormalities. CONCLUSIONS: Although high-resolution PET appears to be very sensitive in localizing frontal lobe glucose metabolic abnormalities in children with intractable FLE and normal CT/MRI scans, the significance of extrafrontal metabolic disturbances requires further study; these may represent additional epileptogenic areas, effects of diaschisis, seizure propagation sites, or secondary epileptogenic foci.

Adolescent↗

PubMed1997

Clinical role of positron emission tomography in children with tuberous sclerosis complex.

We evaluated the clinical role of positron emission tomography (PET) in 23 children with tuberous sclerosis complex. Mean age of the children when first scanned was 3.3 years. Mean age when seizures began was 8.7 months. All, except three, were at least mildly developmentally delayed. PET images were visually analyzed and compared to computed tomography (CT), magnetic resonance imaging (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study was normal. One of the studies was performed with a low resolution early generation scanner at age 7 months; the other infant was 2 days old. Twenty-one of the 23 children had focal or multifocal cortical hypometabolism. Some hypometabolic cortical regions on PET did not show corresponding abnormalities on CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET provides additional localizing information to CT and MRI in patients with tuberous sclerosis complex. However, because of the normally low cerebral glucose metabolism in infancy, PET may give false negative findings if performed prior to about 1 year of age. The usefulness of glucose metabolism PET in most patients with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI abnormalities are unifocal or unilateral, and surgery is being contemplated, more detailed evaluation with PET may help to determine if contralateral tubers are present and evaluate the functional integrity of the brain as a whole.

Brain↗

PubMed1997

Glucose metabolism in the human cerebellum: an analysis of crossed cerebellar diaschisis in children with unilateral cerebral injury.

Using high-resolution positron emission tomography (PET), we have recently described the normal pattern of glucose utilization in 11 anatomical regions of the human cerebellum. In the present study, we evaluated the phenomenon of crossed cerebellar diaschisis in 40 patients (mostly children) with unilateral cerebral injury sustained at various periods of brain development. Diaschisis refers to a functional impairment at a remote site following injury to an anatomically connected area of brain and, presumably due to a loss of afferent input to the remote site. Of the 40 patients, 11 had sustained their cerebral injury prenatally, 7 in the perinatal period (+/- 24 hours of birth), and 22 postnatally (1 day to 15 years). Crossed cerebellar hypometabolism was seen in 22 patients; symmetric cerebellar metabolism was found in 16 subjects. The presence of crossed cerebellar hypometabolism was typically associated (75% of cases) with a postnatal injury, while symmetric cerebellar metabolism was seen only in patients with injury occurring prior to 4 weeks of age (13 of the 16 had prenatal or perinatal insults). A third pattern of cerebellar metabolism, consisting of paradoxical crossed cerebellar hypermetabolism, was seen in two patients; both had sustained their cerebral injury at 4 months of age. These findings suggest the presence of considerable plasticity, which is dependent on age at injury, in the cerebrocerebellar pathway of developing brain.

Adolescent↗

PubMed1997

Language and motor functions activate calcified hemisphere in patients with Sturge-Weber syndrome: a positron emission tomography study.

This study examines whether or not in Sturge-Weber syndrome hypoperfused brain areas that are affected by calcification continue to retain some function and participate in language and motor activations. [15O]-Water positron emission tomography (PET) was used for brain mapping of these functions in two patients with extensive unilateral calcification and hypoperfusion and in one patient with calcification and hypoperfusion restricted to the left posterior region. Task-related regional cerebral blood flow changes suggest that (1) hypoperfused areas may become activated during language and motor performance, and (2) progressive calcification in Sturge-Weber syndrome is associated with functional reorganization in the language and motor domains. Interhemispheric reorganization appears to be more pronounced for language than for motor functions.

Adolescent↗

PubMed1997

Landau-Kleffner syndrome: metabolic abnormalities in temporal lobe are a common feature.

Landau-Kleffner syndrome (acquired epileptic aphasia) is characterized by language regression following normal acquisition of language skills, accompanied by epileptiform abnormalities on the electroencephalogram (EEG) with or without clinical seizures. Continuous spikes and waves during slow wave sleep may be seen on the EEG, but are not required to make the diagnosis. Structural neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI) is typically normal. We have evaluated 17 children (aged 2.4 to 10.6 yr) with Landau-Kleffner syndrome using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in order to determine whether there are metabolic abnormalities common to this syndrome. Patients were awake for the uptake period of FDG, and the EEG was monitored. On a visual analysis of the PET images, patients showed metabolic abnormalities in the temporal lobes. Two children had focal hypermetabolism in the left temporal cortex, one of whom also showed right temporal cortex hypometabolism. The remaining patients (n = 15) showed bilateral temporal hypometabolism, and comparison of these patients with a neurologically normal age-matched control group (n = 8) demonstrated significantly reduced glucose metabolism bilaterally in middle temporal gyrus (P < .02). In addition, other cortical regions displayed hypometabolism, although these regions were not consistently abnormal in all patients. The finding of temporal lobe abnormalities in all Landau-Kleffner syndrome patients suggests that temporal lobe structures are important in the pathophysiology of this syndrome, whereas the presence of additional cortical abnormalities in many patients indicates that extensive brain functional disturbances are common.

Analysis of Variance↗

PubMed1996

Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography.

Positron emission tomography (PET) of brain glucose utilization is highly sensitive in detecting focal cortical abnormalities in patients with infantile spasms even when the computed tomographic (CT) and magnetic resonance imaging (MRI) scans are normal. Of 110 infants with spasms evaluated for potential surgical intervention during an 8-year period, we encountered 18 infants (7 males, 11 females; age range, 10 mo to 5 yr) with a common metabolic pattern on positron emission tomography (PET) consisting of bilateral hypometabolism in the temporal lobes. CT and MRI scans did not reveal any focal abnormalities in the 18 infants. Video-electroencephalographic monitoring indicated either bilateral or multifocal epileptogenicity, or failed to show any epileptic focus, so that none of the 18 infants were considered candidates for resective surgery. These patients were then enrolled in a prospective study aimed at determining long-term outcome in the presence of bilateral temporal PET hypometabolism. Analysis of outcome in 14 of the 18 subjects (follow-up period, 10 mo to 10 yr 5 mo; mean, 3 yr 11 mo +/- 2 yr 4 mo [SD]) revealed the following: (1) all had severe developmental delay and had failed to gain significant milestones; (2) language development had been minimal or absent; (3) 10 of the 14 met the DSM-IV criteria for autistic disorder. Our findings indicate that patients with infantile spasms and bitemporal glucose hypometabolism on PET comprise a relatively homogeneous group and are typically not candidates for cortical resection. The long-term outcome of these infants is particularly poor and the majority are autistic.

Autistic Disorder↗

PubMed1996

Pediatric Rasmussen encephalitis: social communication, language, PET and pathology before and after hemispherectomy.

This prospective case study examined social communication (i.e., formal thought disorder, cohesion), language, positron emission tomography glucose utilization, and neuropathology in four children with Rasmussen encephalitis who achieved seizure control following right hemispherectomy. Prior to hemispherectomy, all four children had illogical thinking, loose associations, cohesive deficits, and impaired performance on formal language tests. Their postoperative improvement in social communication and language appeared to be related to age of onset, duration of illness, and postsurgical reversibility of hypometabolism in the nonresected prefrontal cortex. These changes were not associated with increase in IQ scores. The variability in the type and extent of pathologic change across subjects reflected the severity and duration of the illness. The study's findings imply that early surgical intervention might have mitigated certain aspects of the social communication and linguistic deficits found in these children.

Adolescent↗

PubMed1996

Hemispherectomy for intractable seizures in children: a report of 58 cases.

Fifty-eight children who underwent anatomical, functional, or modified anatomical hemispherectomy for intractable seizures from 1986 to 1995 were evaluated for seizure control, motor function, and complications. Age at surgery ranged from 0.3 to 17.3 years (median 2.8 years). Twenty-seven anatomical, 27 functional, and 4 modified anatomical hemispherectomies were performed. Seizure control and motor function in the 50 patients with more than 1 year follow-up revealed a 90% or better reduction in seizure frequency in 44/50 (88%) overall: 19/22 (86%) anatomical, 23/26 (89%) functional, and 2/2 modified anatomical. Motor function of the preoperatively hemiparetic extremities was improved or unchanged postoperatively in 38/50 (76%) of the patients. Complications included one intraoperative death, one late death from shunt obstruction managed elsewhere, late postoperative seizure breakthrough requiring reoperation and further disconnection in 5/27 functional hemispherectomy patients, mild cerebrospinal fluid infections in 3/27 anatomical hemispherectomy patients, and hydrocephalus requiring shunting in 3/27 functional hemispherectomy patients. A review of the literature and comparison of techniques is presented.

Adolescent↗

PubMed1996

A high-yield and simplified procedure for the synthesis of alpha-[11C]methyl-L-tryptophan.

Alpha-[11C]methyl-L-tryptophan (AMT) has been synthesized by stereoselective methylation with [11C]methyl iodide of the lithium-enolate generated by treating dimethyl 2(S), 3a(R), 8a(S)-(+)-hexahydro-8(phenylsulfonyl)pyrrolo [2, 3-b]indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at -55 degrees C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 +/- 12% (decay corrected) in 30-35 min from [11C]methyl iodide. At end of synthesis (EOS), 138 +/- 35 mCi (n = 24) of product was collected with a specific activity of ca. 1-1.3 Ci/mumol (EOS) (4-5 Ci/mumol @ EOB) starting from 1.5 Ci (EOB) of [11C]CO2.

Carbon Radioisotopes↗

PubMed1996

Cerebral metabolism following neonatal or adult hemineodecortication in cats: I. Effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography.

In the cat, cerebral hemispherectomy sustained neonatally results in a remarkable degree of recovery and/or sparing of function as compared with the effects of a similar lesion but sustained in adulthood. We have proposed that this effect is due to a combination of reduced neuronal loss within partially denervated structures and a lesion-induced reorganization of corticofugal projections arising from the remaining intact hemisphere in the neonatally lesioned animal. The current study was designed to assess the physiological consequences of these anatomical changes utilizing [14C]2-deoxy-D-glucose autoradiography. A total of 17 adult cats were studied. Seven animals served as intact controls, five received a left cerebral hemineodecortication as neonates (NH; mean age 11.4 days), and five sustained the same lesion in adulthood (AH). Histological analysis indicated that the lesion was very similar between the two age groups and essentially represented a unilateral hemineodecortication. Local CMRglc (LCMRglc; mumol 100 g-1 min-1) values were calculated for 50 structures bilaterally and indicated that in the remaining intact contralateral (right) cerebral cortex (including all areas measured), AH cats exhibited a significantly (p < 0.05) lower level of LCMRglc (ranging from 20 to 72 mumol 100 g-1 min-1) than NH (ranging from 49 to 81 mumol 100 g-1 min-1). In comparison, the rates of NH cats within the cerebral cortex were very similar to those seen in intact animals (ranging from 48 to 119 mumol 100 g-1 min-1). Ipsilateral to the lesion in AH cats, the structures spared by the resection, including the basal ganglia and thalamus, exhibited LCMRglc rates of between 23 and 69 mumol 100 g-1 min-1, which were significantly lower (p < 0.05) than in NH cats (range 47-72 mumol 100 g-1 min-1). Considering all structures, both age-at-lesion groups exhibited a lower level of metabolism compared with similar measurements for intact control animals (LCMRglc range 45-75 mumol 100 g-1 min-1). However, this depression of glucose metabolism was more pronounced in the AH cats (p < 0.05). These results indicate that following neonatal hemineodecortication, LCMRglc is maintained at a higher level in many regions of the brain than in animals that sustain the same resection in adulthood. This higher level of glucose metabolism in NH animals suggests that the lesion-induced anatomical reorganization of structures not directly injured by the lesion plays a functional role that is probably responsible for the greater degree of recovery and/or sparing of function in these early lesioned cats.

Aging↗

PubMed1996

Etiologic classification of infantile spasms in 140 cases: role of positron emission tomography.

The classification of infantile spasms into symptomatic, cryptogenic, and idiopathic subgroups depends on clinical examination and available diagnostic technology. Positron emission tomography (PET) of glucose utilization is a powerful tool in detecting brain malformations (particularly cortical dysplasia) in infants with spasms. We analyzed etiologic data from 140 such infants, 78 girls and 62 boys, ages 2 months to 4 years 10 months (mean, 17 months). All had been evaluated extensively in one of two major medical centers. It should be emphasized that our referral population is biased toward infants with intractable spasms who fail to show a structural lesion. Seven patients had neurocutaneous syndromes, two had chromosomal abnormalities, two had inborn errors of metabolism, and one each had craniosynostosis or Menkes syndrome. Computed tomography and/or magnetic resonance imaging detected lesions in another 29 infants (20.7%) who did not have a specific disease or syndrome. Without the benefit of PET, the total number of symptomatic cases was 42 (30.0%). One infant, classified as idiopathic, had normal development and PET. In 97 cryptogenic cases, PET uncovered unifocal abnormalities in 30 and multifocal abnormalities in 62. Diffuse PET abnormalities, which did not provide specific etiologic information, were seen in three infants. Another two infants had normal PET scans. Thus, with the benefit of PET, the number of symptomatic cases rose dramatically from 42 (30.0%) to 134 (95.7%). The majority of unifocal and multifocal abnormalities on PET are believed to represent dysplastic lesions.

Brain↗

PubMed1996

Glucose metabolism in the human cerebellum: anatomical-functional correlations.

Functional maturation of human cerebellar structures was previously difficult to evaluate with positron emission tomography (PET) because of scanner resolution. Only vermis and cerebellar hemispheres could be reliably identified with 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET. In the present study, we have used a new high resolution PET system, the Siemens EXACT-HR, to study, in depth, the patterns of glucose metabolism in various cerebellar structures. Due to the orientation of the cerebellar fissures which are important landmarks, the largest number of regions could be identified when the cerebellar regions were displayed on coronal planes. The high resolution PET images, together with magnetic resonance imaging (MRI) data and standard atlases, now allow identification of the following cerebellar structures: anterior vermis, posterior vermis, dentate nucleus, anterior lobe, posterior quadrangular lobule, superior semilunar lobule, inferior semilunar, gracile, and biventer lobules, tonsil, and cerebellar white matter. These cerebellar regions are displayed in an atlas format together with magnetic resonance images to allow easy identification. The present study is a prerequisite for detailed PET analyses of cerebellar metabolism in children with diseases of the cerebellum.

Adolescent↗

PubMed1995

New Spielmeyer-Vogt variant with granular inclusions and early brain atrophy.

Three females in 2 families were originally diagnosed with Spielmeyer-Vogt disease (SVD). The clinical course was different from SVD, with vision well preserved until age 10 years, and learning rather than visual difficulties the marker at the onset. Later, regression was unusually rapid, including global dementia, blindness, aphasia, and finally loss of self-feeding and ambulation between ages 12-18 years. MRI scan in patient 3 documented brain atrophy between ages 8-10 years. Position Emission Tomography (PET) scanning with fluorodeoxyglucose in patients 2 and 3 showed diffusely decreased or absent cortical glucose metabolism, comparable at ages 12 and 18 years, respectively, to the results found in the oldest typical SVD case tested at age 29 years. Fine granular inclusions, instead of the expected fingerprint inclusions, were demonstrated by electron microscopy of lymphocytes, conjunctiva, and skin. Usual markers on chromosome 16p12 were not present in the first family tested. The clinical course, with nonspecific initial behavior difficulties, late onset of visual decline followed by fast global regression, progressive brain atrophy, decreased cortical glucose utilization as shown by PET scanning, and granular tissue inclusions, suggest a genetic variant of SVD.

Adult↗