Search PubMed⌕ Search

Biomedical subjects

G Di Chiro

Publications and source records attributed to G Di Chiro.

At least 37 records · Page 2Linked to original sources

Regional cerebral blood flow imaging with 99mTc-bicisate SPECT in asymmetric Parkinson's disease: studies with and without chronic drug therapy.

Regional cerebral perfusion was assessed in six patients with asymmetric Parkinson's disease (PD) of mild to moderate severity and in six matched normal subjects using 99mTc-bicisate single photon emission computed tomography (SPECT). Regional activity was normalized to whole-brain activity. Each subject was studied twice, separated by 15.2 +/- 9.2 and 18.0 +/- 4.8 days in normals and PD patients, respectively. There was low intrasubject scan-rescan variability in normals, with all regions showing an average intrasubject difference in repeat studies of < 3%. In PD patients after chronic oral antiparkinsonian drugs had been withdrawn, as compared with normal subjects, there was increased perfusion in the caudate and lenticular nuclei contralateral to the worst affected extremities. This increased basal ganglia perfusion was attenuated by chronic oral therapy. The clinical relevance of these changes is indicated by the high positive correlation between various measures of clinical PD severity and the lenticular perfusion. These differences in basal ganglia perfusion measured with 99mTc-bicisate SPECT in mild to moderate, asymmetric PD may be secondary to increased metabolic demand resulting from alterations of synaptic activity.

Adult↗

6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys.

Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is a desirable therapeutic strategy in Parkinson's disease. We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[18F]fluoro-L-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O-methyl-6-[18F]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD formation was attended by increased production of other metabolites, in particular 6-[18F]fluorodopamine (6FDA), 6-[18F]fluorodihydroxyphenylacetic acid (FDOPAC), 6-[18F]fluorohomovanillic acid (FHVA) and [18F]-sulfated conjugates (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high-dose nitecapone increased contrast of cerebral 18F uptake and retention between regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic innervation. 18F uptake contrast was also improved between structures known to possess an intermediate dopaminergic innervation, including the upper brainstem, frontal and temporal lobes, versus sparsely innervated regions. This increased contrast was secondary to decreased activity in sparsely innervated structures and not to increased activity in highly innervated structures. Contrast was correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the main 6FD metabolite which can cross the blood brain barrier. We conclude that nitecapone is an effective inhibitor of COMT in non-human primates. This inhibition results in increased 6FD flux through other catabolic pathways. Because of decreased OMFD formation, however, COMT inhibition improves the specificity of 6FD-PET and facilitates in-vivo detection of a wide range of dopaminergic innervation densities in cerebral structures.

Animals↗

Neuroimaging of juvenile pilocytic astrocytomas: an enigma.

PURPOSE: To present the imaging, metabolic, and clinical data obtained in five patients with juvenile pilocytic astrocytomas (JPAs) and discuss the paradoxical neuroimaging findings. MATERIALS AND METHODS: Five patients with JPAs who had undergone structural imaging and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were studied. Normalized glucose utilization rates (GURs) in the tumor were compared with GURs in histopathologically verified low-grade astrocytomas and high-grade tumors. RESULTS: All JPAs enhanced markedly after administration of contrast medium. Their glucose metabolism was significantly (P < .001) higher than that of low-grade astrocytomas and was similar to that of anaplastic astrocytomas. All patients with JPAs were in stable condition and showed no evidence of disease progression despite contrast enhancement and high tumoral glucose metabolism. CONCLUSION: The paradoxical FDG PET findings and enhancement at structural imaging might reflect the unusual vascularity of pilocytic tumors, and the increased GUR might be related to expression of the glucose transporter.

Adolescent↗

Histopathologic correlates of abnormal water diffusion in cerebral ischemia: diffusion-weighted MR imaging and light and electron microscopic study.

PURPOSE: To correlate the findings on diffusion-weighted magnetic resonance (MR) images with the cytologic and histologic findings in ischemic tissue. MATERIALS AND METHODS: A photochemical model of cerebral infarction in rats was studied with diffusion- and T2-weighted MR imaging. The development of lesions was followed from 20 minutes to 5 days after the onset of ischemia. Apparent water diffusion coefficient (ADC) maps were calculated and correlated with light and electron microscopic findings. RESULTS: T2-weighted images clearly showed vasogenic edema but did not enable distinction between areas with cellular damage and the surrounding edematous regions. In contrast, the ADC, which was elevated in nonischemic edematous regions, was diminished in areas with histologic evidence of ischemic damage or necrosis. In the core of the infarct, the ADC became elevated when electron microscopy revealed cellular lysis. CONCLUSION: Diffusion-weighted images may help ascertain the extent of cellular damage and death after stroke.

Animals↗

T1 and T2 of ferritin at different field strengths: effect on MRI.

Nuclear magnetic relaxation times T1 and T2 were measured in ferritin solutions at field strengths from 0.04 to 1.5 T. T1 was relatively constant, but 1/T2 increased linearly with field strength, in agreement with earlier MRI observations in the monkey brain. This finding supports the theory that ferritin is responsible for T2 shortening in brain nuclei containing iron. The linear dependence of 1/T2 on magnetic field is unique and not explained by present theories of the magnetic properties of ferritin.

Animals↗

Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance.

Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy.

Adolescent↗

Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing.

A unilateral supratentorial lesion may cause hypometabolism in the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). We analyzed glucose metabolism, measured by PET-FDG, in the posterior fossa in 67 patients (78 PET studies) with primary unilateral supratentorial brain tumors selected for visually obvious metabolic asymmetry in the cerebellar hemispheres. We found that glucose utilization was 17% lower in the contralateral cerebellar cortex (compared with the ipsilateral one), consistent with the selection criterion, and 19% lower in the ipsilateral pons, wherein lie the first order synapses of the corticopontocerebellar pathway. This finding helps to validate the prevalent view that cerebellar diaschisis is due to interruption of afferent input from the corticopontocerebellar pathway. However, glucose metabolism in the contralateral dentate nucleus was relatively preserved--only 2% less than the ipsilateral dentate. This "dentate sparing" suggests preservation of afferent input to the largest of the deep cerebellar nuclei from the Purkinje cells in the cortex, despite interruption of the major excitatory input to the Purkinje cells.

Adolescent↗

PET-fluorodeoxyglucose of cranial and spinal neuromas.

Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.

Adolescent↗

Computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose in multiple system atrophy and pure autonomic failure.

We studied 45 patients who had autonomic failure with computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose to characterize the neuroimaging features of multiple system atrophy and pure autonomic failure and determine the utility of these techniques in distinguishing multiple system atrophy from pure autonomic failure. There were 30 patients with multiple system atrophy and 15 with pure autonomic failure. In the multiple system atrophy group, eight patients had mainly cerebellar signs, seven extrapyramidal and 15 had combinations of cerebellar and extrapyramidal signs. Cerebellar atrophy on computerized tomography and magnetic resonance imaging, signal hypointensity in the posterolateral putamen on magnetic resonance imaging and a generalized reduction in glucose utilization rate with positron emission tomography with [18F]fluorodeoxyglucose, were the main findings and were seen only in the patients with multiple system atrophy. Decreased glucose utilization (hypometabolism) was most prominent in the cerebellum, brainstem, striatum and frontal and motor cortices. These results indicate clear differences, using neuroimaging studies, between multiple system atrophy and pure autonomic failure.

Atrophy↗

In vivo study of NMDA-sensitive glutamate receptor by fluorothienylcyclohexylpiperidine [correction of fluorothienylcycloexylpiperidine], a possible ligand for positron emission tomography.

As a preliminary to positron emission tomography (PET) studies of excitatory amino acid neurotransmission, N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors of mice and rats were labelled in vivo with [3H]fluorothienylcyclohexylpiperidine [corrected] (FTCP), which binds to the phencyclidine site of the NMDA receptor. After intravenous injection, the half-life of clearance of authentic FTCP from blood was 4.2 min in mice, 12 min in rats and 45 min in a rhesus monkey. In rodent brain, the specific binding of [3H]FTCP, 10 min after intravenous injection, was 10-20% of the total binding and no regional differences were observed. However, if animals were treated with NMDA intraperitoneally (0.68 mmol/kg), 10 min before injection of [3H]FTCP, a three- to five-fold increase in specific binding was observed in hippocampus, cerebral cortex and striatum but not in cerebellum. Thus, specific binding of [3H]FTCP in vivo revealed the physiological status of the NMDA receptor; in fact, preliminary PET studies with [18F]FTCP in monkeys indicated increased binding after activation of NMDA receptors. These data suggest that PET with [18F]FTCP can be a tool to evaluate physiological or pathological modifications of the function of NMDA receptors.

Animals↗

Positron emission tomography of pituitary macroadenomas: hormone production and effects of therapies.

Positron emission tomography with [18F]fluorodeoxyglucose (FDG) was carried out in 24 patients with pituitary macroadenomas (32 studies) to assess the glucose utilization of these tumors in vivo. The adenoma metabolic index, which is the ratio of FDG uptake of tumor to a whole brain slice, was calculated. Comparisons were made between tumor uptake of FDG and hormone secretion and response to therapies. In each positron emission tomography study, the macroadenoma could be easily identified visually as an area of increased FDG uptake near the region of the sella. FDG uptakes were highest for nonfunctional adenomas, and the prolactin, growth hormone, and thyroid-stimulating hormone-producing groups displayed similar levels of glucose metabolism. The adenoma metabolic index for all tumors averaged 1.3, ranging from 0.3 for a thyroid-stimulating hormone adenoma to 3.5 for a nonfunctional tumor. Tumors did not exhibit metabolic rates that could characterize the type of hormone produced. Recurrent macroadenomas displayed metabolism similar to tumors not operated on, whereas irradiated adenomas showed lower glucose uptake than nonirradiated tumors. Drug therapy with bromocriptine or the long-acting somatostatin analogue octreotide also decreased the glucose utilization of the tumor. There was no correlation between the amount of hormone produced and the adenoma metabolic index when a group of tumors was analyzed. Patients scanned more than once, however, demonstrated changes in hormone levels that changed or did not change in parallel with tumor metabolism. Thus, positron emission tomography offers the potential capability for predicting and defining the growth of pituitary adenomas. This may be of particular value when plasma hormone assays and conventional imaging techniques prove inadequate for monitoring patient response to therapy.

Adenoma↗

Increased glucose metabolism in the medulla of patients with palatal myoclonus.

Hypertrophic degeneration of the inferior olivary nuclei is the pathologic substrate for palatal myoclonus, but the physiologic correlate of this finding is uncertain. Using the 2-[18F]fluoro-2-deoxy-D-glucose and PET method, we determined the local cerebral metabolic rate of glucose utilization in seven patients with palatal myoclonus (following stroke or infection, or idiopathic), one patient with oculopalatal myoclonus (following a stroke affecting the brainstem), and nine normal subjects. The metabolism of glucose in the medulla of the patients with palatal myoclonus was significantly greater than that of the normal subjects. This may well have been due to increased metabolism of the inferior olivary nuclei. Glucose metabolism in the medulla of the patient with oculopalatal myoclonus was normal. These findings suggest that the inferior olivary nuclei, or a region of the brainstem encompassing the inferior olivary nuclei, are hypermetabolic in palatal myoclonus and may be the generators of the involuntary movements in palatal myoclonus.

Adult↗

MR phase imaging and cerebrospinal fluid flow in the head and spine.

Motion of the cerebrospinal fluid (CSF) in and around the brain and spinal cord was examined in healthy subjects and in a number of patients with abnormalities of the CSF circulation. The pulsatile motion of the CSF was determined by spin echo phase (velocity) imaging, sometimes in combination with gradient echo phase contrast cine. Differences in flow patterns across CSF spaces were observed: flow reversal in the cerebellomedullary cistern and lumbar area relative to cervical CSF, and in the posterior versus the anterior subarachnoid space in the spinal canal. Flow communication was demonstrated in known communicating cysts or cavities. Differences in flow were also noted across spinal narrowing or block, and across the walls of a variety of cystic lesions in the brain and spinal cord. MR phase imaging of CSF flow provides pathophysiological information of potential clinical importance for the assessment of diseases affecting the CSF circulation.

Brain↗

Pituitary microadenomas: a PET study.

Twenty cases of surgically verified pituitary microadenoma (17 with Cushing disease and three with acromegaly) were studied with positron emission tomography (PET) with use of fluorine-18-2-fluorodeoxyglucose (FDG). The diagnostic results were compared with those of other modalities, namely, computed tomography (CT), magnetic resonance (MR) imaging, and, in the cases of Cushing disease, simultaneous bilateral inferior petrosal sinus sampling (SIPS). The PET results showed 12 positive readings and one questionable reading, compared with seven positive readings and one questionable reading for CT (18 cases studied) and 13 positive and two questionable MR imaging readings. PET complemented MR imaging, in the sense that five of the positive PET readings were negative or questionable at MR imaging. PET studies of 20 healthy control subjects showed no false-positive cases, whereas other studies of healthy subjects with contrast material-enhanced CT and MR imaging have yielded, respectively, 20% and 15% positive readings, with findings suggestive of silent or occult adenomas.

Adenoma↗

Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths.

The authors measured in vivo signal intensity on magnetic resonance (MR) images and postmortem iron concentrations in the brains of three young and two old rhesus monkeys. T2-weighted MR imaging was done at 0.5, 1.5, 2.0, and 4.7 T. Relative assessment of iron concentration was made from the optical density of brain sections stained with the Perls' method intensified with diaminobenzidine. MR imaging and optical density measurements were made in the centrum semiovale (white matter) and in four gray matter areas: the insular cortex, caudate nucleus, putamen, and globus pallidus, the latter three of which accumulate significant iron deposits with age. High optical density and decreased signal intensity were found in these areas, and the inverse correlation between gray matter/white matter signal ratio and optical density was in good agreement with the theory of T2 shortening caused by diffusion of water through magnetic inhomogeneities. However, the dependence of T2 shortening on field strength was not quadratic, as expected for paramagnetic iron, but instead showed a marked leveling off at higher field strengths. This magnetic "saturation" is explainable by antiferromagnetism and superparamagnetism of the ferritin core and has been observed in ferritin solutions at low temperatures. Similar observations at body temperature are needed before the iron-ferritin explanation for T2 shortening can be considered proved.

Aging↗

Hemiballismus: study of a case using positron emission tomography with 18fluoro-2-deoxyglucose.

A 64-year-old man had right-sided persistent hemiballismus. Cerebral computed tomography (CT) and 0.5-T magnetic resonance imaging (MRI) showed no abnormalities, but 1.5-T MRI showed decreased signal intensity of the putamina, greater on the left than on the right. The subthalamic area was normal on CT and MRI. Positron emission tomography with 18fluoro2-deoxyglucose showed marked hypometabolism of the left putamen (60% of the right) and hypermetabolism of the left parietal lobe (138% of the right). The decreased metabolism of the left putamen may indicate a reduction in neuronal firing. The pathophysiology of the hemiballismus in this case may be loss of tonic inhibition of the lateral globus pallidus from the putamen, leading in turn to greater inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, and less inhibition of the thalamus and motor cortex, and thus allowing expression of the ballistic movements.

Adolescent↗

On the origin of paramagnetic inhomogeneity effects in blood.

Hydrogen, sodium, and fluorine (added F-) NMR spectra of venous and oxygenated blood were measured. The fluorine resonance was seen as a single peak in both samples, and all three resonances exhibited the same deoxy-oxy shift. Because F- exchanges slowly across the red cell membrane, and because sodium is 95% extracellular, these results suggest that the intra-extracellular field difference delta B is less than 0.1 ppm. A small value of delta B tends to rule out transmembrane exchange as an important contributor to relaxation in MRI of blood and hematomas. However, the broadening of the resonances with deoxygenation, by 0.3-0.4 ppm, indicates that both intra- and extracellular gradients are of comparable and sufficient magnitude to produce the T2-weighted hypointensity seen in clinical magnetic resonance images of hematomas at high fields.

Blood↗