Brain perfusion assessed by 99mTc-ECD SPECT imaging in pediatric patients with neurally mediated reflex syncope.

BACKGROUND: The involvement of cardiogenic and neurogenic mechanisms in neurally mediated reflex syncope is well documented. In our previous studies in patients with neurally mediated reflex syncope, we have found evidence for differential regulation of the noradrenergic receptors in tilt-positive and tilt-negative patients. The present work concentrates on the observations of differences in regional brain perfusion using brain SPECT via injecting the patient at the completion of the tilt test. METHODS AND RESULTS: The following study was designed to assess the reduction and regional differences in cerebral blood flow by means of SPECT using technetium-99m labeled V-oxo-1,2-N1ethylenedylbisl-cysteine diethylester (ECD) in patients with an injection during tilt testing. Twenty patients with NMS were included in the study with a mean age of 12.2 years (age range; 8-16 years). HUT was positive in 10 patients and negative in 10 patients. When tilt (+) and tilt (-) were evaluated together, regional cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical areas with highest variability of perfusion index in left frontoparietal cortex. The lowest perfusion index values were observed in the left anterior frontal region followed by the left prefrontal-frontoparietal-anterior, parietal-orbito frontal, and anterior temporal regions where perfusion is predominantly supplied via the anterior and middle cerebral arteries, while these differences did not reach statistical significance in a single dominant region compared to the other regions examined using ANOVA (P > 0.05) with this sample size. Decreases in [99mTc]ECD uptake were more widespread regionally on the left hemisphere than were decreases in right side of the brain. However when tilt- and tilt+ groups were compared, perfusion was significantly lower in the right periinsular posterior parietal and temporal regions (P < 0.05) in tilt + group. CONCLUSION: These tilt induced regional differences in brain perfusion suggest the distinct roles of middle cerebral artery dominant territory-related vasodepressor compensation mechanisms in neurally mediated reflex syncope phenomena where cerebral lateralization of cardiac control and insular ischemia may play an important role.

Influence of exogenous estrogen administration on serum CA-125 originating from the endometrium.

OBJECTIVES: The purpose of the study is to assess the endometrial contribution of serum CA-125 using exogenous estrogen administration by ruling out ovarian activity. A randomized, controlled, prospective study was designed to assess the endometrial contribution of serum CA-125 and its influence from estrogen administration in menopausal women. METHODS: Twenty menopausal women with intact uterus and ovaries (study group) and 10 cases with previous total hysterectomy with intact ovaries (control group) were included in the study. The mean age of subjects in the study and control groups were similar at 53 +/- 1.9 (S.D.) and 51 +/- 2.7 years. The length of menopause in the study and control groups were also similar at 61.0 +/- 18 and 52.6 +/- 26.5 months, respectively. Group 1 consisted of 10 randomly selected cases and five controls who received 15 days of 50 microg/day transdermal 17beta-estradiol (TE). Group 2 consisted of the next randomly selected 10 cases and five controls who had 15 days of transdermal 100 microg/day 17beta-estradiol (Estraderm-Ciba) administration. Serum CA-125 and estradiol were measured at day 0, 15 by radioimmunoassay (RIA). RESULTS: Serum mean CA-125 levels increased significantly in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6%, respectively (P=0.03 and P=0.05, respectively). Interestingly, the increase in serum estradiol levels accompanied this change only in group 2. CONCLUSIONS: These results suggest that endometrial CA-125 secretion to serum is dependent on the dose of administered exogenous estrogen.

Is increased D2 receptor availability associated with response to stimulant medication in ADHD.

The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test,p<0.05) as a function of methylphenidate therapy in patients with ADHD in all four regions of the striatum. When the relation between therapy response and D2 availability was investigated, we observed that the higher the baseline D2 levels were, the higher the response rate was (detected as the percentage reduction of hyperactivity scores and Conners Teacher Rating Scale scores), while no such trend was observed between the initial D2 binding levels and the response in attention-deficit scores. Results indicate that in non-drug treated children with ADHD, higher D2 receptor availability is observed at baseline which is down-regulated back to reported near-normal values after methylphenidate therapy. The effect of methylphenidate on D2 receptor levels in patients with ADHD is similar to that observed in healthy adults; a down-regulation phenomenon within 0 to 30%. In addition, initially higher values of D2 availability seem to indicate better response to methylphenidate therapy in ADHD.

PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease.

OBJECTIVE: To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). METHODS: We used the radiotracer [11C]-WIN 35,428 and PET. Regional striatal dopamine transporter binding was measured in the caudate, anterior putamen, and posterior putamen of six patients with L-dopa-responsive stage 2 PD, six patients with PSP, and six age-comparable healthy controls. RESULTS: In patients with idiopathic PD, the most marked abnormality was observed in the posterior putamen (77% reduction), whereas transporter density in the anterior putamen (60% reduction) and the caudate (44% reduction) was less affected. Unlike the patients with PD, the PSP group showed a relatively uniform degree of involvement in the caudate (40% reduction), anterior putamen (47% reduction), and posterior putamen (51% reduction). When posterior putamen/caudate ratios were calculated, these values were significantly lower in patients with PD than they were in patients with PSP (p = 0.0008) and the control group (p < 0.0001). CONCLUSIONS: Patients with PD have a more pronounced loss of dopamine transporters in the posterior putamen due to a subdivisional involvement of nigrostriatal dopaminergic projections in idiopathic PD. This technique is useful in the determination of neurochemical changes underlying PD and PSP, thus differentiating between them.

Functional imaging of neurotransmitter systems in movement disorders.

PET and SPECT enable the direct measurement of components of the dopaminergic and other systems in the living human brain and offer unique opportunity for the in vivo quantification of the dopaminergic function in PD and other movement disorders. The need to establish the early and differential diagnosis of PD is increasingly important given the recent evidence that early pharmacologic intervention may slow progression of this progressive degenerative disease. Accordingly, imaging with PET and SPECT using specific neuromarkers has been increasingly important to biochemically identify the loss of specific neurotransmitters, their synthesizing enzymes and their receptors in movement disorders. Through the parallel development of new radiotracers, kinetic models and better instruments, PET and SPECT technology is enabling investigation of increasingly more complex aspects of the human brain neurotransmitter systems. This paper summarizes the results of different PET-SPECT studies used to evaluate the various elements of the dopamine system in the human brain with PET and intends to introduce the newly emerging specific tracers and their applications to clinical research in movement disorders.

Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine.

The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor.

Evaluation of renal function following treatment with extracorporeal shock wave lithotripsy (ESWL): the use of whole-kidney, parenchymal and pelvic transit times.

The aim of this prospective study was to assess the efficacy of using whole-kidney, mean parenchymal and pelvic transit times to evaluate renal function following treatment with extracorporeal shock wave lithotripsy (ESWL). Fifteen patients were evaluated 24-48 h before and after ESWL therapy using 99Tcm-DTPA renal scintigraphy. Using deconvolution analysis, whole-kidney, mean parenchymal and pelvic transit times were calculated and the pre-ESWL values were compared with the post-ESWL values. In both kidneys, there were no significant changes in the glomerular filtration rate or relative renal uptake when compared with the pre-ESWL values. The mean whole-kidney transit time of the tracer did not change significantly during the post-ESWL period. In the treated kidney, the mean post-ESWL parenchymal transit time was significantly increased (P < 0.05), while the mean pelvic transit time was significantly decreased (P < 0.05). In the untreated kidney, there were no significant changes in any of these parameters. We conclude that the dual use of parenchymal and pelvic transit times is more sensitive than the mean whole-kidney transit time and other measures, such as glomerular filtration rate and relative renal uptake, for the assessment of outcome of therapy and other related post-ESWL changes.

Dual isotope myocardial perfusion SPECT in the detection of coronary artery disease: comparison of separate and simultaneous acquisition protocols.

A time-saving dual isotope acquisition protocol was carried out for the simultaneous assessment of stress and rest myocardial perfusion, and the diagnostic value of the technique was evaluated using coronary angiography results as a reference. Fifty-five patients undergoing coronary angiography before surgery were included in the study. Stress tests were applied, either with a treadmill (25 patients) or dobutamine infusion (30 patients in 5-40 micrograms/kg/min doses). All patients received 3 mCi of thallium-201 at rest. Stress tests were applied 30 minutes later, and at peak stress 7 mCi of 99mTc-MIBI was administered. A dual isotope SPECT study was carried out one hour after the administration of 99mTc-MIBI. Tracer doses were optimised with phantom studies, and the down-scatter of each radioisotope on the other data was investigated. In 30 patients, 10 minutes after the 201Tl injection a separate rest 201Tl acquisition was also performed, to compare the data with dual acquisition. 201Tl rest imaging SPECT data was evaluated by segmental analysis according to coronary artery regions. In 55% of the segments stress defects were observed. Similar results were obtained for the detection of defect reversibility; i.e. stress MIBI/rest 201Tl (75%) and stress MIBI/simultaneous 201Tl (78%). The overall sensitivity and specificity of simultaneous dual isotope SPECT with respect to coronary angiography results were 88% and 84%, respectively. A good correlation and no significant difference was observed between the two acquisition methods. However, the simultaneous acquisition protocol has many advantages, i.e. halving the acquisition time, shortening the overall decision-making time, and decreasing unmatched stress-rest artifacts.

Regional cerebral blood flow in Angelman syndrome.

A patient with typical features of Angelman syndrome--a genetically inherited disorder involving developmental delay, ataxia, episodes of paroxysmal laughter and brachiocephaly--was studied with single-photon emission tomography. Hypoperfusion found in the left frontal and left temporoparietal regions can provide insights into the functional cerebral pathology, which may be due to a disturbance of the developmental process related to a chromosomal abnormality.