Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
3.
Eur J Radiol ; 82(3): 512-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23079049

ABSTRACT

OBJECTIVES: The nerve ending problem is one of the major causes for diabetic feet. In this work, we explored the feasibilities of using high frequency ultrasound (US) in nerve ending problem evaluation for patients with diabetic foot. METHODS: The endings of the medial branch of deep peroneal nerves (mbDPN) were interrogated by US, and the nerve conduction characters were studied in a cohort of 19 clinically diagnosed diabetic feet patients and a control group of healthy volunteers. RESULTS: Distinct echoic appearances were consistently detected between the mbDPN nerves of diabetic feet patients and healthy volunteers. In healthy volunteers, hypoechoic bands were readily observed at the anatomical locations of mbDPNs. However, these hypoechoic bands of the mbDPNs were not clear in the diabetic feet patients, and the surfaces of the mbDPNs appeared obscure and irregular in these patients relative to those of healthy volunteers. In addition, the US echoes of mbDPN in patients with diabetic feet were more heterogeneous than those in healthy volunteers. The mean diameters of mbDPNs were 1.3±0.4 mm in patients with diabetic foot and 0.8±0.2 mm in the control group (P<0.05). Finally, results from the nerve conduction studies (NCS) showed abnormalities in patients with diabetic feet syndrome. CONCLUSION: High frequency US can be a useful modality for evaluating nerve ending problems in diabetic feet patient; and the mbDPN enlargement, obscurity, surface irregularity and heterogeneity in echo can serve as the markers indicating nerve ending problems in the diabetic feet patients under ultrasound interrogation.


Subject(s)
Diabetic Foot/complications , Diabetic Foot/diagnostic imaging , Nerve Endings/diagnostic imaging , Peroneal Nerve/diagnostic imaging , Peroneal Neuropathies/complications , Peroneal Neuropathies/diagnostic imaging , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Ultrasonography
4.
Eur J Nucl Med Mol Imaging ; 39(10): 1609-17, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22806059

ABSTRACT

PURPOSE: Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. (123)I-MIBG can detect these innervation changes. METHODS: Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and (123)I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. RESULTS: Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 ± 0.75, and the mean wash-out rate was 8.6 ± 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 ± 0.70 versus 2.8 ± 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 ± 9.9 % vs. 17 ± 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 ± 0.59 vs. 2.9 ± 0.50, p = 0.007). CONCLUSION: MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, (123)I-MIBG scintigraphy can detect cardiac denervation in ATTR patients before signs of amyloidosis are evident on echocardiography.


Subject(s)
3-Iodobenzylguanidine , Amyloidosis/diagnostic imaging , Cardiomyopathies/diagnostic imaging , Heart/innervation , Radiopharmaceuticals , Sympathetic Nervous System/diagnostic imaging , Aged , Amyloidosis/complications , Cardiomyopathies/etiology , Female , Gated Blood-Pool Imaging , Humans , Male , Middle Aged , Myocardial Perfusion Imaging , Nerve Endings/diagnostic imaging , Ultrasonography
5.
PLoS One ; 6(8): e23393, 2011.
Article in English | MEDLINE | ID: mdl-21853125

ABSTRACT

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups.


Subject(s)
Biological Evolution , Birds/anatomy & histology , Dinosaurs/anatomy & histology , Skull/anatomy & histology , Animals , Cranial Nerves/anatomy & histology , Cranial Nerves/diagnostic imaging , Dinosaurs/genetics , Ear, Inner/anatomy & histology , Ear, Inner/diagnostic imaging , Fossils , Nerve Endings/diagnostic imaging , Phylogeny , Radiography , Skull/diagnostic imaging , Skull/innervation
6.
Mov Disord ; 26(2): 327-30, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-20939078

ABSTRACT

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long-standing PD has not yet been specifically explored. Therefore, we performed [(123)I]-FP-CIT single photon emission computed tomography (SPECT) in 15 patients with very long-standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [(123)I]-FP-CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD.


Subject(s)
Brain/diagnostic imaging , Dopamine/metabolism , Nerve Endings/diagnostic imaging , Neurons/diagnostic imaging , Parkinson Disease/diagnostic imaging , Aged , Brain/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Humans , Male , Middle Aged , Nerve Endings/metabolism , Neurons/metabolism , Parkinson Disease/metabolism , Tomography, Emission-Computed, Single-Photon
7.
Int J Radiat Oncol Biol Phys ; 59(2): 426-35, 2004 Jun 01.
Article in English | MEDLINE | ID: mdl-15145159

ABSTRACT

PURPOSE: To (a) locate neurovascular bundles (NVB) on pelvic CT and (b) retrospectively evaluate relationships between radiation dose to structures putatively involved in prostate brachytherapy-induced erectile dysfunction (ED) and incidence of postbrachytherapy ED. METHODS AND MATERIALS: (a) Right/left NVB were identified on nine prostate MRIs. Structures visible on MRI and CT were cross-referenced. Cross-sectional area of each NVB was measured. (b) All patients treated with implant alone and whose treatment was planned on Variseed (Varian Medical Systems, Palo Alto, CA), with follow-up of >12 months were included; n = 41. Median follow-up was 20 months. All patients were potent (+/- sildenafil) before implant (erection sufficient for intercourse). The right/left NVB (using results from part "a"), penile bulb, and right/left crus were outlined on postimplant CT. Volumes and doses to these structures were calculated. RESULTS: (a) On prostate MRI, NVB was consistently located where the prostate border bends away from the levator ani, at the gland's smallest radius of curvature. Average area of the circle best encompassing the NVB = 0.27 cm(2); diameter was 0.58 cm. (b) 11 of 41 (27%) patients had ED; 30 of 41 were potent (15 with sildenafil). There was no significant difference between potent/impotent patients in isotope, age, diabetes, hypertension, follow-up, or volume of prostate, bulb, right/left NVB, or right/left crus. There was a relationship between smoking and ED (p = 0.05). There was a relationship between bulb %D90 and ED: >10% 67% (4 of 6) vs. <10% 20% (7 of 35) (p = 0.03), which remained when controlling for smoking. There was no relationship between dose to left NVB and potency. There was paradoxical decreased risk of ED with right NVB %V100 >60% (p = 0.019), and right NVB %D60 >100% (p = 0.003). There was no relationship between dose to right/left crus and ED. CONCLUSIONS: A reliable method for localizing NVB on CT is demonstrated. There is no increased risk of prostate brachytherapy-induced ED with increasing dose to crus or NVB at the doses given in this study. There is a possible dose-response relationship between dose to the bulb and risk of ED.


Subject(s)
Brachytherapy/adverse effects , Erectile Dysfunction/etiology , Nerve Endings/diagnostic imaging , Prostate/blood supply , Prostate/innervation , Prostatic Neoplasms/radiotherapy , Dose-Response Relationship, Radiation , Erectile Dysfunction/diagnostic imaging , Erectile Dysfunction/drug therapy , Humans , Magnetic Resonance Imaging/methods , Male , Nerve Endings/radiation effects , Pelvis , Penis/radiation effects , Piperazines/therapeutic use , Prostate/diagnostic imaging , Purines , Retrospective Studies , Sildenafil Citrate , Sulfones , Tomography, X-Ray Computed , Vasodilator Agents/therapeutic use
8.
Jpn Circ J ; 65(4): 349-52, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11316138

ABSTRACT

Four patients had the clinical features of 'ampulla cardiomyopathy', consisting of acute-onset transient left ventricular apical akinesis with basal normokinesis, normal coronary angiogram, ST-segment elevation and subsequent giant T wave inversion, which mimicked acute coronary syndrome, the onset of which occurred shortly after extreme mental stress. Myocardial necrosis was minimal, although 2 patients showed elevated serum catecholamine levels in the acute phase. Each patient underwent serial cardiac radionuclide single-photon emission computed tomography of myocardial functional sympathetic innervation, fatty acid metabolism and perfusion using I-123-metaiodobenzyl-guanidine (MIBG), I-123-beta-metyl-iodophenyl pentadecanoic acid (BMIPP) and thallium-201 (201Tl), respectively. In the acute phase, MIBG and BMIPP imaging showed an uptake defect in the apical region, whereas 201Tl uptake was mildly decreased. When assessed semi-quantitatively, the MIBG images had higher defect scores from the acute phase throughout the year of observation compared with BMIPP, and 201Tl. These observations suggest that the primary cause of ampulla cardiomyopathy is related to a disturbance of the cardiac sympathetic innervation.


Subject(s)
Autonomic Nervous System Diseases/etiology , Heart Conduction System/physiopathology , Stress, Psychological/complications , Ventricular Dysfunction, Left/etiology , 3-Iodobenzylguanidine/pharmacokinetics , Aged , Autonomic Nervous System Diseases/physiopathology , Catecholamines/blood , Chest Pain/etiology , Disasters , Emotions , Family Relations , Fatty Acids/metabolism , Female , Heart/diagnostic imaging , Humans , Iodine Radioisotopes , Iodobenzenes , Middle Aged , Myocardium/metabolism , Nerve Endings/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Stress, Psychological/physiopathology , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/pathology
9.
J Nucl Med ; 41(12): 2069-76, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11138694

ABSTRACT

UNLABELLED: [18F](+)-4-fluorobenzyltrozamicol (FBT), which selectively binds to the vesicular acetylcholine transporter in the presynaptic cholinergic neuron, has previously been shown to be a useful ligand for the study of cholinergic terminal density in the basal ganglia with PET. The goal of this study was to assess the test-retest variability of [18F]FBT and PET measurements under baseline conditions in the basal ganglia. METHODS: After approval from the Animal Care and Use Committee, 6 rhesus monkeys underwent a series of 2 [18F]FBT PET scans (time between scans, 32-301 d) under isoflurane anesthesia. Each scan was initiated on the bolus injection of the radiotracer and consisted of 26 frames acquired during 180 min. Arterial blood samples were collected over the course of each scan to determine the metabolite-corrected arterial input function. Tissue time-activity curves were obtained from the scan data by drawing regions of interest over the basal ganglia and cerebellum. The distribution volume ratio for the basal ganglia was then determined for each scan by taking the ratio of the basal ganglia (specific binding) to cerebellum (nonspecific binding) distribution volume. Distribution volumes were derived using the Logan graphic analysis technique as well as a standard 3-compartment model. Additionally, the radioactivity concentration ratio was calculated as the ratio of the average [18F]FBT concentration in the basal ganglia to that in the cerebellum during the last half of the study (85-170 min). The constant K1, determined using the standard 3-compartment model, was used as an index of blood flow changes between studies. RESULTS: For all subjects, the test-retest variability was less than 15% for the distribution volume ratio and 12% for the radioactivity concentration ratio. Good agreement was found between the distribution volume ratio calculated using the graphic technique and the standard 3-compartment model. Using K1 as an index, the variability in blood flow seen in both the basal ganglia and the cerebellum was significantly reduced in their ratio. CONCLUSION: These results show the reproducibility of [18F]FBT and PET measurements in the basal ganglia.


Subject(s)
Brain/diagnostic imaging , Cholinergic Fibers/diagnostic imaging , Fluorine Radioisotopes , Fluorobenzenes , Nerve Endings/diagnostic imaging , Piperidines , Radiopharmaceuticals , Tomography, Emission-Computed , Animals , Basal Ganglia/diagnostic imaging , Cerebellum/diagnostic imaging , Macaca mulatta , Male , Reproducibility of Results
10.
Am J Cardiol ; 84(5): 568-74, 1999 Sep 01.
Article in English | MEDLINE | ID: mdl-10482157

ABSTRACT

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.


Subject(s)
Ephedrine/analogs & derivatives , Heart Failure/diagnostic imaging , Heart/innervation , Norepinephrine/analogs & derivatives , Sympathetic Nervous System/diagnostic imaging , Sympathomimetics , Tomography, Emission-Computed , Blood Pressure/physiology , Carbon Radioisotopes , Coronary Circulation/physiology , Female , Heart/diagnostic imaging , Heart Failure/physiopathology , Heart Rate/physiology , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Nerve Endings/diagnostic imaging , Nerve Endings/physiopathology , Pressoreceptors/physiopathology , Reference Values , Reflex/physiology , Sympathetic Nervous System/physiopathology
11.
J Comput Assist Tomogr ; 23(1): 25-33, 1999.
Article in English | MEDLINE | ID: mdl-10050803

ABSTRACT

PURPOSE: Our goal was to demonstrate the feasibility of an in vivo noninvasive method for imaging spinal cord cholinergic terminals using (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) and PET. METHOD: In vitro and in vivo experiments in rats were conducted to demonstrate the specific binding characteristics, localization, and time course of [3H]FBT binding in the spinal cord. PET imaging was then performed on seven rhesus monkeys. RESULTS: The rat studies demonstrate high specific binding in the spinal cord with a distribution coinciding with the known distribution of cholinergic terminals. In vivo tracer concentrations in the spinal cord and basal ganglia were of the same magnitude. With use of [18F]FBT and PET in the rhesus monkey, the spinal cord was clearly visualized, with tracer concentration in the spinal cord being approximately one-fourth of that seen in the basal ganglia. CONCLUSION: This work demonstrates the feasibility of imaging cholinergic terminals in vivo in the spinal cord using [18F]FBT and PET.


Subject(s)
Cholinergic Fibers/diagnostic imaging , Fluorobenzenes , Nerve Endings/diagnostic imaging , Piperidines , Spinal Cord/diagnostic imaging , Tomography, Emission-Computed , Animals , Autoradiography , In Vitro Techniques , Macaca mulatta , Male , Radioligand Assay , Rats , Rats, Sprague-Dawley
12.
Ann Neurol ; 43(3): 387-90, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9506557

ABSTRACT

Positron emission tomography (PET) and carbon-11-labeled 2B-carbomethoxy-3B-(4-fluorophenyl)tropane (11C-CFT or 11-WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non-DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C-CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation.


Subject(s)
Dopamine/metabolism , Fetal Tissue Transplantation , Mesencephalon/embryology , Nerve Endings/metabolism , Parkinson Disease, Secondary/surgery , Tomography, Emission-Computed , Animals , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Corpus Striatum/surgery , Female , Nerve Endings/diagnostic imaging , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/diagnostic imaging , Rats , Rats, Sprague-Dawley
13.
J Nucl Cardiol ; 4(1 Pt 1): 35-41, 1997.
Article in English | MEDLINE | ID: mdl-9138838

ABSTRACT

BACKGROUND: Accumulation of 131I-labeled metaiodobenzylguanidine ([131I]MIBG), a radiolabeled norepinephrine analog, is reduced in infarcted myocardium, suggesting loss of cardiac sympathetic nerve viability. Histopathologic studies, however, indicate that the nerve endings ae morphologically intact. Experiments were therefore designed to determine the mechanism of reduced MIBG accumulation. METHODS AND RESULTS: Desipramine, a specific blocker or neuronal norepinephrine reuptake, was used to separate the portions of total myocardial [131I]MIBG accumulation attributable to neuronal and nonneuronal uptake mechanisms. Sixteen dogs underwent circumflex coronary artery occlusion for 60 minutes followed by a 5-hour reperfusion. [131I]MIBG was injected intravenously 1 hour after reperfusion. The left ventricle was removed and incubated in triphenyltetrazolium chloride to identify infarcted and viable myocardium within the zone at risk. Preliminary studies in sham-operated dogs showed that pretreatment with desipramine (5 mg/kg) reduced [131I]MIBG accumulation 4 hours after injection to 38.9% of untreated controls. Chemical sympathectomy by topical phenol resulted in a similar decrease in [131I]MIBG accumulation (to 45.7% of normal), and desipramine did not produce further inhibition of [131I]MIBG accumulation over that produced by phenol alone, indicating that the inhibitory effect of desipramine on neuronal accumulation of [131I]MIBG was essentially complete. In dogs undergoing ischemia-reperfusion, myocardial samples from infarcted and viable postischemic areas showed 64.5% +/- 11.85 and 84.7% +/- 9.1% of normal [131I]MIBG activity, respectively (both, p < 0.01 vs normal area, n = 9). With desipramine pretreatment (n = 7), accumulation of [131I]MIBG decreased in all areas. Neuronal accumulation was reduced uniformly in infarcted, viable postischemic, and normal areas by 30% to 35% compared with sham-operated controls. In contrast, nonneuronal accumulation was only 39.3% in infarcted areas and 84.6% in viable postischemic areas compared with normal areas, and these decreases accounted entirely for the reduced total [131I]MIBG accumulation. CONCLUSIONS: Reduced [131I]MIBG accumulation in infarcted myocardium after 60 minutes of ischemia and 5 hours of reperfusion is attributable to a deficit in nonneuronal accumulation and not to decreased accumulation by sympathetic nerves.


Subject(s)
Heart Conduction System/diagnostic imaging , Iodine Radioisotopes , Iodobenzenes , Myocardial Ischemia/diagnostic imaging , Myocardial Reperfusion , Radiopharmaceuticals , Sympathetic Nervous System/diagnostic imaging , Sympatholytics , 3-Iodobenzylguanidine , Adrenergic Uptake Inhibitors/pharmacology , Animals , Coloring Agents , Desipramine/pharmacology , Dogs , Female , Heart Conduction System/metabolism , Heart Conduction System/pathology , Heart Conduction System/physiopathology , Heart Ventricles/metabolism , Heart Ventricles/pathology , Injections, Intravenous , Iodine Radioisotopes/pharmacokinetics , Iodobenzenes/pharmacokinetics , Male , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Ischemia/metabolism , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Myocardium/metabolism , Nerve Endings/diagnostic imaging , Nerve Endings/pathology , Nerve Endings/physiopathology , Phenol , Phenols , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Sympathectomy, Chemical , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/pathology , Sympathetic Nervous System/physiopathology , Sympatholytics/pharmacokinetics , Tetrazolium Salts
14.
J Nucl Med ; 37(7): 1186-92, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8965196

ABSTRACT

UNLABELLED: The PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared. METHODS: Carbon-11-CFT (WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), 11C-CCT (RTI-131, 2 beta-carbomethoxy-3 beta-(4-monochlorophenyl)tropane), and 11C-CDCT (dichloropane, 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane) were evaluated as imaging probes for dopamine neurons in five normal and in two MPTP-treated cynomolgus monkeys (macaca fascicularis) using a high-resolution PET imaging system (PCR-I). RESULTS: For 11C-CFT, the specific binding ratio (as defined by the ratio of radioactivity levels in striatum versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in putamen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control animals. In MPTP-treated monkeys the corresponding ratios were 1.4 +/- 0.1 in caudate and 1.5 +/- 0.1 in putamen at 60 min and 1.3 +/- 0.1 in caudate and 1.4 +/- 0.3 in putamen at 90 min. For the monochloro analog of CFT, 11C-CCT, the ratios in control caudate and putamen were 2.7 +/- 0.4 and 3.4 +/- 0.3, respectively, at 60 min and 3.7 +/- 0.5 and 4.4 +/- 0.6, respectively, at 90 min. In MPTP-treated animals, corresponding ratios were 1.4 +/- 0.4 and 1.5 +/- 0.3 at 60 min and 1.4 +/- 0.4 and 1.6 +/- 0.4 at 90 min. The dichloro analog of CFT, CDCT, which has the highest affinity for the dopamine transporter, generated the lowest ratios in control brains, 2.3 +/- 0.4 in caudate and 2.4 +/- 0.5 in putamen at 60 min. In one MPTP-treated monkey, the corresponding ratios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with 11C-CFT, both 11C-CCT and 11C-CDCT were less selective and had high uptake in the thalamus. CONCLUSION: The present results clearly indicate that 11C-CFT is a useful ligand for monitoring dopamine neuronal degeneration.


Subject(s)
Brain/diagnostic imaging , Dopamine Uptake Inhibitors , Dopamine/metabolism , Nerve Endings/chemistry , Parkinson Disease, Secondary/diagnostic imaging , Tomography, Emission-Computed , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Carbon Radioisotopes , Cocaine/analogs & derivatives , Female , Macaca fascicularis , Male , Nerve Endings/diagnostic imaging , Parkinson Disease, Secondary/chemically induced
15.
Q J Nucl Med ; 39(4 Suppl 1): 49-54, 1995 Dec.
Article in English | MEDLINE | ID: mdl-9002749

ABSTRACT

Norepinephrine (NE) is one of the many biologically active substances that are metabolized by the lung. The norepinephrine uptake in the lung has been widely investigated in animal studies in order to detect abnormalities of the endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a radioactive tracer that shares several metabolic pathways with NE; it has been used instead NE or both in animal and in human studies for the same purposes. It has been definitely demonstrated that MIBG lung uptake following intravenous administration is a reliable marker of minimal endothelial cell lesions and it allows one to investigate several conditions involving damage to the lung vasculature such as adult respiratory distress syndrome, post-actinic lung fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a tracer of the neuroadrenergic system of the airways, once it has been deposited in the whole branches of the bronchial tree. With this in mind we evaluated the feasibility of the administration of MIBG in radioaerosol form. We first performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus demonstrating that aerosolization does not significantly modify the stability of the tracer. We then compared both the lung clearance curves and the scintigraphic images in two groups of normal subjects who respectively underwent [123I]MIBG and 99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27 minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve endings of the airways. The pulmonary distribution of both tracers was homogeneous, as demonstrated by the correspondence of the values for the aerosol penetration index in both groups of subjects. Such results warrant further research and pharmacologic tests.


Subject(s)
Iodine Radioisotopes , Iodobenzenes , Lung Diseases/diagnostic imaging , Radiopharmaceuticals , 3-Iodobenzylguanidine , Adrenergic Fibers/diagnostic imaging , Adult , Aerosols , Animals , Biomarkers , Bronchi/innervation , Chromatography , Drug-Related Side Effects and Adverse Reactions , Endothelium, Vascular/metabolism , Feasibility Studies , Humans , Injections, Intravenous , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/analysis , Iodine Radioisotopes/pharmacokinetics , Iodobenzenes/administration & dosage , Iodobenzenes/analysis , Iodobenzenes/pharmacokinetics , Lung/drug effects , Lung/innervation , Lung/metabolism , Metabolic Clearance Rate , Nerve Endings/diagnostic imaging , Norepinephrine/metabolism , Pulmonary Fibrosis/diagnostic imaging , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/analysis , Radiopharmaceuticals/pharmacokinetics , Respiratory Distress Syndrome/diagnostic imaging , Technetium Tc 99m Pentetate
16.
Article in English | MEDLINE | ID: mdl-7605590

ABSTRACT

Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11C-S-Nomifensine (11C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11C-NMF asymmetries, suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss, and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism.


Subject(s)
Cerebral Cortex/diagnostic imaging , Dopamine/metabolism , Norepinephrine/metabolism , Parkinson Disease/diagnostic imaging , Tomography, Emission-Computed , Aged , Carbon Radioisotopes , Cerebellum/diagnostic imaging , Cerebellum/metabolism , Cerebellum/physiopathology , Cerebral Cortex/metabolism , Cerebral Cortex/physiopathology , Functional Laterality , Humans , Magnetic Resonance Imaging , Nerve Endings/diagnostic imaging , Nerve Endings/metabolism , Nomifensine , Parkinson Disease/metabolism , Parkinson Disease/physiopathology , Putamen/diagnostic imaging , Putamen/metabolism , Putamen/physiopathology
17.
Exp Neurol ; 126(2): 305-9, 1994 Apr.
Article in English | MEDLINE | ID: mdl-7925829

ABSTRACT

We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.


Subject(s)
Carbon Radioisotopes , Caudate Nucleus/diagnostic imaging , Cocaine/analogs & derivatives , Dopamine/metabolism , Motor Activity , Parkinson Disease, Secondary/diagnostic imaging , Putamen/diagnostic imaging , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Caudate Nucleus/pathology , Caudate Nucleus/physiopathology , Cocaine/metabolism , Cocaine/pharmacokinetics , Dopamine/analysis , Nerve Endings/diagnostic imaging , Nerve Endings/pathology , Parkinson Disease, Secondary/pathology , Parkinson Disease, Secondary/physiopathology , Putamen/pathology , Putamen/physiopathology , Tomography, Emission-Computed/methods
18.
Brain Res ; 597(1): 151-4, 1992 Nov 27.
Article in English | MEDLINE | ID: mdl-1477728

ABSTRACT

[18F]-6-Fluoro-beta-fluoromethylene-m-tyrosine ([18F]FFMMT) was evaluated as a potential imaging agent for dopamine nerve terminals using positron emission tomography (PET). Biodistribution and time course of this tracer in mice after i.p. injection was consistent with the distribution of dopamine. PET imaging studies involving rhesus macaques showed specific uptake in the dopamine-rich caudate-putamen region. This specific localization was blocked by inhibiting the enzyme L-aromatic amino acid decarboxylase and the transport of the tracer into brain was shown to be stereospecific. These results show the promise of L-[18F]FFMMT as a PET tracer in monitoring degeneration of the CNS dopamine system.


Subject(s)
Dopamine/physiology , Nerve Endings/diagnostic imaging , Tomography, Emission-Computed , Animals , Female , Fluorine Radioisotopes , Macaca mulatta , Male , Mice , Mice, Inbred ICR , Tissue Distribution/physiology , Tyrosine/analogs & derivatives , Tyrosine/pharmacokinetics
19.
Int J Rad Appl Instrum A ; 43(8): 969-77, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1330983

ABSTRACT

18F-labeled (E)-beta-fluoromethylene-DL-m-tyrosine (FMMT) was prepared by the direct reaction of FMMT with [18F]acetylhypofluorite (AcOF) resulting into three product isomers. Extensive 1H, 13C and 19F-NMR spectroscopic analysis identify these products to be 2-fluoro, 6-fluoro-FMMT and 2,6-difluoro-FMMT. The HPLC isolated radiochemical EOB yields of these products were 22, 25 and 14%, respectively, based on starting [18F]AcOF. The specific activity at the end of a synthesis time of an hour was ca 200 mCi/mmol. With the possible advantage of "metabolic trapping" in dopamine nerve terminals via covalent binding to MAO and reduced metabolite formation, [18F]F-FMMT may potentially be the optimal PET tracer for CNS dopamine nerve terminals.


Subject(s)
Brain/physiology , Dopamine/physiology , Nerve Endings/diagnostic imaging , Tomography, Emission-Computed , Tyrosine/analogs & derivatives , Brain/diagnostic imaging , Tyrosine/chemical synthesis
20.
Neurol Neurochir Pol ; 13(2): 165-7, 1979.
Article in Polish | MEDLINE | ID: mdl-377120

ABSTRACT

The authors observed 88 patients (18 women and 70 men) aged 16 to 61 years with lack of lumbar vertebral arch fusion (spina bifid occulta without spinal cord involvement). In 63 cases the clinical symptom complex was that of sciatic pains, in the remaining 25 cases no neurological defect was found. In 63 cases operation was done and 45 of them intervertebral disc prolapse was found. The decision to operate was based on the refractoriness and intensity of pain, presence of neurological defect and radiculography performed in 36 cases. It is stressed that such high proportion (51%) of cases with spina bifida coexistent with lumbar disc prolapse calls for a careful analysis of the cause of pain in patients with spina bifida.


Subject(s)
Lumbar Vertebrae/abnormalities , Spina Bifida Occulta/diagnostic imaging , Adolescent , Adult , Female , Humans , Intervertebral Disc Displacement/complications , Lumbar Vertebrae/surgery , Male , Middle Aged , Nerve Endings/diagnostic imaging , Radiography , Spina Bifida Occulta/complications , Spina Bifida Occulta/surgery
SELECTION OF CITATIONS
SEARCH DETAIL
...