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PubMed2003

Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

Animals↗
PubMed1998

Patent foramen ovale size and embolic brain imaging findings among patients with ischemic stroke.

BACKGROUND AND PURPOSE: Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ischemic stroke patients. METHODS: As part of the Northern Manhattan Stroke Study, 95 patients with first ischemic stroke over age 39 underwent transesophageal echocardiography (TEE) for evaluation of a cardiac source of embolism. The stroke subtype was determined by modified NINDS Stroke Data Bank criteria. Stroke subtype and MRI/CT imaging data were evaluated blind to the presence of a PFO. These findings were compared between two groups: patients with medium to large PFO (> or =2 mm) and small (<2 mm) or no PFO. RESULTS: Of the 95 patients who underwent TEE, 31 (33%) had a PFO. The frequency of PFO was significantly greater among patients with cryptogenic infarcts (19 of 42; 45%) compared with patients with determined cause of stroke (12 of 53, 23%; P=0.02). Medium to large PFOs were found more often among cryptogenic strokes than among infarcts of determined cause (26% versus 6%; P=0.04). Superficial infarcts occurred more often in the group with larger PFOs than in the group with small or no PFOs (50% versus 21%; P=0.02). Patients with medium or large PFOs more frequently had occipital and infratentorial strokes (57% versus 27%; P=0.02). CONCLUSIONS: Stroke patients with larger PFOs show more brain imaging features of embolic infarcts than those with small PFOs. Larger PFOs may be more likely to cause paradoxical embolization and may help explain the stroke mechanism among patients with no other definite cause.

Aged↗
PubMed2006

Synthesis and evaluation of radioiodinated (S,S)-2-(alpha-(2-iodophenoxy)benzyl)morpholine for imaging brain norepinephrine transporter.

PURPOSE: Abnormality of the brain norepinephrine transporter (NET) has been reported in several psychiatric and neuronal disorders. Since NET is an important target for the diagnosis of these diseases, the development of radiopharmaceuticals for imaging of brain NET has been eagerly awaited. In this study, we synthesized (S,S)-2-(alpha-(2-iodophenoxy)benzyl)morpholine [(S,S)-IPBM], a derivative of reboxetine iodinated at position 2 of the phenoxy ring, and evaluated its potential as a radiopharmaceutical for imaging brain NET using SPECT. METHODS: (S,S)-(123/125)I-IPBM was synthesized in a halogen exchange reaction. The affinity and selectivity of (S,S)-IPBM for NET was measured by assaying the displacement of (3)H-nisoxetine and (S,S)-(125)I-IPBM from the binding site in rat brain membrane, respectively. The biodistribution of (S,S)-(125)I-IPBM was also determined in rats. Furthermore, SPECT studies with (S,S)-(123)I-IPBM were carried out in the common marmoset. RESULTS: (S,S)-(125)I-IPBM was prepared with high radiochemical yields (65%) and high radiochemical purity (>98%). (S,S)-IPBM showed high affinity and selectivity for NET in the binding assay experiments. In biodistribution experiments, (S,S)-(125)I-IPBM showed rapid uptake in the brain, and the regional cerebral distribution was consistent with the density of NET. The administration of nisoxetine, a selective NET-binding agent, decreased the accumulation of (S,S)-(125)I-IPBM in the brain, but the administration of selective serotonin transporter and dopamine transporter binding agents caused no significant changes in the accumulation. Moreover, (S,S)-(123)I-IPBM allowed brain NET imaging in the common marmoset with SPECT. CONCLUSION: These results suggest that (S,S)-(123)I-IPBM is a potential SPECT radiopharmaceutical for imaging brain NET.

Animals↗
PubMed2003

Radiopharmaceuticals for single-photon emission computed tomography brain imaging.

In the past 10 years, significant progress on the development of new brain-imaging agents for single-photon emission computed tomography has been made. Most of the new radiopharmaceuticals are designed to bind specific neurotransmitter receptor or transporter sites in the central nervous system. Most of the site-specific brain radiopharmaceuticals are labeled with (123)I. Results from imaging of benzodiazepine (gamma-aminobutyric acid) receptors by [(123)I]iomazenil are useful in identifying epileptic seizure foci and changes of this receptor in psychiatric disorders. Imaging of dopamine D2/D3 receptors ([(123)I]iodobenzamide and [(123)I]epidepride) and transporters [(123)I]CIT (2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane) and [(123)I]FP-beta-CIT (N-propyl-2-beta-carboxymethoxy-3-beta(4-iodophenyl)-nortropane has proven to be a simple but powerful tool for differential diagnosis of Parkinson's and other neurodegenerative diseases. A (99m)Tc-labeled agent, [(99m)Tc]TRODAT (technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino] ethanethiolato(3-)]oxo-[1R-(exo-exo)]-), for imaging dopamine transporters in the brain has been successfully applied in the diagnosis of Parkinson's disease. Despite the fact that (123)I radiopharmaceuticals have been widely used in Japan and in Europe, clinical application of (123)I-labeled brain radiopharmaceuticals in the United States is limited because of the difficulties in supplying such agents. Development of (99m)Tc agents will likely extend the application of site-specific brain radiopharmaceuticals for routine applications in aiding the diagnosis and monitoring treatments of various neurologic and psychiatric disorders.

Animals↗
PubMed2001

Dopamine and cognitive functioning: brain imaging findings in Huntington's disease and normal aging.

Recent brain imaging studies in Huntington's disease (HD) and normal aging suggest a relationship between central dopaminergic neurotransmission and cognitive performance. Results demonstrate substantial losses in dopamine (DA) function in both HD and aging. Moreover, HD patients and older adults show deficits across multiple cognitive domains, including episodic memory, speed of processing, and executive functioning. Although few studies are available at present, there is converging evidence that multiple measures of pre- and postsynaptic DA biochemistry are (a) highly interrelated, and (b) strongly associated with the cognitive deficits that accompany HD and aging. There is also emerging evidence that DA neurotransmission influences cognitive performance independent of HD or age. In general, the research reviewed in this article indicates that the nigrostriatal DA system is an important component of a frontostriatal circuitry that is critically involved in cognitive functioning.

Aging↗
PubMed2004

Fetal trauma: brain imaging in four neonates.

The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age ( n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound ( n=4), computed tomography (CT) ( n=1) and post-mortem magnetic resonance imaging (MRI) ( n=1). Pathology findings were correlated with the imaging findings ( n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage ( n=1), subdural hematoma ( n=1), brain edema with inversion of the diastolic flow ( n=1) and severe ischemic changes ( n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered.

Abdominal Injuries↗
PubMed2000

Application of PET-MRI registration techniques to cat brain imaging.

UNLABELLED: In positron emission tomography (PET) studies of diseased animals, it is very useful to have accurate anatomical information as a reference. In human studies, anatomical information is usually obtained from magnetic resonance imaging (MRI) of the subject with retrospective registration of the subject's PET image to the MRI. A number of PET-MRI registration techniques are used for this purpose. However, the utility of these methods has not been tested for animals image registration. This paper studies the feasibility of applying two currently used human brain PET-MRI registration techniques to cat brain images. METHODS: Three cats were anesthetized with isoflurane gas, and PET images were acquired with H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET scans were acquired consecutively within the same day while the cat remained fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the cats in a 4.7 T unit. The PET images were registered to MRI using two human brain registration techniques: a semi-automatic method (SAM), which is a two-step method based on the extraction of the midsagittal plane, and an automatic method (AMIR) method that minimizes PET pixel variance within spatially connected segments determined by MRI. RESULTS: T2-weighted MRI provided better structural information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide a structural outline of the brain. The FMZ PET image was registered to MRI satisfactorily using SAM. The striatum visualized in nemonapride PET image re-sliced with the same parameters matched the striatum identified in T2-weighted MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET images in only one of the three cats. The registration error of SAM was estimated to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ-PET to T2-weighted MRI of the cat brain was obtained by a two-step manual registration technique. This will enhance the usefulness of PET in the field of cerebral pathophysiology.

Animals↗
PubMed2004

The processing of verbs and nouns in neural networks: insights from synthetic brain imaging.

The paper presents a computational model of language in which linguistic abilities evolve in organisms that interact with an environment. Each individual's behavior is controlled by a neural network and we study the consequences in the network's internal functional organization of learning to process different classes of words. Agents are selected for reproduction according to their ability to manipulate objects and to understand nouns (objects' names) and verbs (manipulation tasks). The weights of the agents' neural networks are evolved using a genetic algorithm. Synthetic brain imaging techniques are then used to examine the functional organization of the neural networks. Results show that nouns produce more integrated neural activity in the sensory-processing hidden layer, while verbs produce more integrated synaptic activity in the layer where sensory information is integrated with proprioceptive input. Such findings are qualitatively compared with human brain imaging data that indicate that nouns activate more the posterior areas of the brain related to sensory and associative processing, while verbs activate more the anterior motor areas.

Algorithms↗
PubMedDate not supplied

Brain-imaging surrogate markers for detection and prevention of age-related memory loss.

Recent evidence points to the importance of neuropathological and cognitive changes preceding Alzheimer's disease (AD), and clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of AD in people with age-associated memory impairment (AAMI). Studying subjects with few deficits leads to diagnostic heterogeneity and a need for larger samples in order to detect active drug effects. In this report, I review results of recent studies designed to address such issues. Middle-aged and older adults with mild memory complaints were studied using brain imaging and measures of the major known genetic risk for AD, the apolipoprotein E-4 (APOE-4) allele. In a study of positron emission tomography during mental rest, glucose metabolic rates were significantly lower in APOE-4 carriers in brain regions affected by AD. Another study using functional magnetic resonance imaging showed increased brain activation during memory tasks in APOE-4 carriers in similar brain regions. Longitudinal follow-up after 2 yr indicated the potential utility of such brain-imaging measures, combined with genetic-risk information, as surrogate markers in treatment trials for AAMI to prevent further cognitive decline. Current development focuses on novel technologies using positron emission tomography to directly image the neuritic plaques and neurofibrillary tangles of AD in order to provide more specific measures of disease progression in future clinical trials.

Aging↗
PubMed1992

Somatosensory evoked responses via electronic brain imaging (EBI).

This study of a series of 40 mildly head injured (concussed) patients suggests that different physiologic pathways underlying the tests done in a six-part resting EEG, and for the 11 evoked electrical potential shifts occurring in the cerebral terrain, are testable. Further work seems likely in order to ascertain which clinical signs and symptoms may be related to specific individual types of recorded electronic brain imaging (EBI) abnormality. Which of the 11 parameters studied, EEG, VER, AER, and SER, would be more or less likely to be abnormal in their individual patterns (as being deviant from normal controls) also remains to be defined. The relationship of these neurophysiologic abnormalities to certain postconcussive symptoms, i.e., headache, dizziness, blurred vision, etc., at this point in time remains to be evaluated more precisely. The authors suggest that further research is necessary in evaluating the clinical use of somatosensory evoked responses as an additional parameter in electronic brain imaging (EBI) technology.

Adolescent↗
PubMed1994

Anatomic standardization: linear scaling and nonlinear warping of functional brain images.

UNLABELLED: An automated method was proposed for anatomic standardization of PET scans in three dimensions, which enabled objective intersubject and cross-group comparisons of functional brain images. METHODS: The method involved linear scaling to correct an individual brain size and nonlinear warping to minimize regional anatomic variations among subjects. In the linear-scaling step, the anteroposterior length and width of the brain were measured on the PET images, and the brain height was estimated by a contour-matching procedure using the midsagittal plane. In the nonlinear warping step, individual gray matter locations were matched with those of a standard brain by maximizing correlation coefficients of regional profile curves determined between predefined stretching centers (predominantly in white matter) and the gray matter landmarks. RESULTS: The accuracy of the brain height estimation was compared with skull x-ray estimations, showing comparable accuracy and better reproducibility. Linear-scaling and nonlinear warping methods were validated using [18F]fluorodeoxyglucose and [15O]water images. Regional anatomic variability on the glucose images was reduced markedly. The statistical significance of activation foci in paired water images was improved in both vibratory and visual activation paradigms. A group versus group comparison following the proposed anatomic standardization revealed highly significant glucose metabolic alterations in the brains of patients with Alzheimer's disease compared with those of a normal control group. CONCLUSION: These results suggested that the method is well suited to both research and clinical settings and can facilitate pixel-by-pixel comparisons of PET images.

Algorithms↗
PubMed2000

[Functional brain imaging: role metabolic coupling between astrocytes and neurons].

Despite the technological sophistication of brain imaging techniques, the precise mechanisms and cell types involved in coupling and in generating metabolic signals are still debated. Recent experimental data on the cellular and molecular mechanisms that underlie the fluorodeoxyglucose (FDG)--based PET imaging point to a critical role of a particular brain cell type, the astrocytes, in coupling neuronal activity to glucose utilization. Indeed, astrocytes possess receptors and re-uptake sites for a variety of neurotransmitters, including glutamate, the predominant excitatory neurotransmitter in the brain. In addition, astrocytic end-feet, which surround capillaries, are enriched in the specific glucose transporter GLUT-1. These features allow astrocytes to "sense" synaptic activity and to couple it with energy metabolism. In vivo and in vitro data support the following functional model: in response to glutamate released by active neurons, glucose is predominantly taken up by astrocytic end-feet; glucose is then metabolized to lactate which provides a preferred energy substrate for neurons. These data support the notion that astrocytes markedly contribute to the FDG-PET signal.

Astrocytes↗
PubMed1984

Performance evaluation of SPRINT, a single photon ring tomography for brain imaging.

SPRINT, a prototype single photon tomograph, has been designed primarily for high-resolution brain imaging in humans with I-123-labeled compounds such as iodoamphetamine, hydroxyiodopropyldiamine (HIPDM), and iodobenzene (IBZ). SPRINT uses a ring of stationary, discrete Nal detectors, and fan-beam sampling is accomplished with a rotating eight-slit aperture ring that acquires a complete projection set in 1/8 revolution. In-plane and cross-plane resolutions are 8mm and 10mm FWHM, respectively, measured on axis. Sensitivity with an 18% energy window is 1000 cprs per microCi/cc for Tc-99m in a 20 cm diameter phantom. A detailed evaluation of system performance has been completed, and preliminary human brain blood flow images have been obtained using HIPDM.

Brain↗
PubMed2004

Determining correspondence in 3-D MR brain images using attribute vectors as morphological signatures of voxels.

Finding point correspondence in anatomical images is a key step in shape analysis and deformable registration. This paper proposes an automatic correspondence detection algorithm for intramodality MR brain images of different subjects using wavelet-based attribute vectors (WAVs) defined on every image voxel. The attribute vector (AV) is extracted from the wavelet subimages and reflects the image structure in a large neighborhood around the respective voxel in a multiscale fashion. It plays the role of a morphological signature for each voxel, and our goal is, therefore, to make it distinctive of the respective voxel. Correspondence is then determined from similarities of AVs. By incorporating the prior knowledge of the spatial relationship among voxels, the ability of the proposed algorithm to find anatomical correspondence is further improved. Experiments with MR images of human brains show that the algorithm performs similarly to experts, even for complex cortical structures.

Aged↗
PubMed2004

The effect of layers in imaging brain function using electrical impedance tomograghy.

Electrical impedance tomography (EIT) has promise for imaging brain function with rings of scalp electrodes, but hitherto human images have been collected and reconstructed using a simple algorithm in which the head was modelled as a homogeneous sphere. The purpose of this work was to assess the improvement in image quality which could be achieved by adding layers to represent the cerebro-spinal fluid (CSF), skull and scalp in the forward model employed by the reconstruction algorithm. Solutions to the forward model were produced analytically and using the linear finite element method (FEM). This was undertaken for computer simulated data when a spherical conductivity change of 10%, radius 5 mm, was moved through 29 positions within a head modelled as four concentric spheres of radius 80-92 mm in order to verify the accuracy of the linear FEM by comparison with the analytical method. Test data were also recorded in a 93.5 mm, spherical, saline-filled tank in which the skull was simulated by a hollow sphere of plaster of Paris, 5 mm thick and a 20 x 20 mm right-cylindrical Perspex object, a 100% conductivity decrease, was moved through 39 positions. The best images were achieved by reconstruction with a four- or three-shell analytical model, giving a spatial accuracy of 5.8 +/- 2.2 mm for computer simulated or 14.0 +/- 5.8 mm for tank data. Mean FWHM was 57 mm and 91 mm in the XY-plane and along the z-axis, respectively. Reconstruction with a homogeneous analytical model gave localization errors greater by about 50-300%, but a reduction in FWHM of about 5% of the image diameter. Unexpectedly, reconstruction with FEM models gave poorer results similar to the analytical homogeneous case. This confirms that addition of shells to the forward model improves image quality as expected with an analytical model for reconstruction, but that the FEM method employed, which used a medium mesh and a linear element computation, requires improvement in order to yield the expected benefits.

Algorithms↗
PubMed1995

Strategic infarcts in vascular dementia. A clinical and brain imaging experience.

The mechanisms of dementia resulting from small deep infarctions are incompletely understood. The thesis underlying the concept of "multi-infarct dementia" is that multiple lesions have a synergistic effect on mental functions, resulting in dementia irrespective of specific location or volume. In this report, we summarize our experience with six patients reported previously along with additional patients examined subsequently, whose clinical features and brain imaging findings allow an alternative formulation for dementia resulting from lacunar stroke. The six initial patients presented with an abrupt change in behavior after acute infarction involving the inferior genu of the internal capsule documented by computed tomography (CT) and magnetic resonance imaging (MRI). The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia were evident in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients using 133xenon regional cerebral blood flow (rCBF) and single photon emission computed tomography (SPECT) showed focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. Perfusion was also defective in the medial and laterial temporal cortex. Important pathways of the limbic system traverse the inferior capsule in the region of the genu. Corticothalamic and thalamocortical fibers form the thalamic peduncles which detach from the internal capsule and enter the thalamus at its rostral and caudal poles and along its dorsal surface. The anterior thalamic peduncle, conveys reciprocal connections between the dorsomedial nucleus and the cingulate gyrus, as well as the prefrontal and orbitofrontal cortex. The inferior thalamic peduncle carries fibers which connect the thalamus with orbitofrontal, insular, and temporal cortex, as well as the amygdala via the ansa peduncularis to the ventral amygdalofugal pathway. Thus, damage to one or both white-matter tracts may occur with infarctions in the region of the inferior genu, causing striking frontal behavioral effects and memory loss in our patients associated with functional deactivation of the ipsilateral frontal and temporal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Infarction↗
PubMed1998

Comparison between 201Tl-chloride and 99Tc(m)-sestamibi SPET brain imaging for differentiating intracranial lymphoma from non-malignant lesions in AIDS patients.

The aim of this study was to compare 201Tl-chloride and 99Tc(m)-sestamibi (MIBI) SPET brain imaging for differentiating brain lymphoma from other intracranial lesions in AIDS patients. Both studies were performed on the same day in 17 AIDS patients with intracranial enhancing lesions on either CT or MRI. Eleven patients underwent brain biopsy and six patients were followed clinically. We calculated the radiopharmaceutical uptake ratio of the lesion to that on the contralateral side with the guidance of CT or MRI findings. Ratios of 1.5 or more were considered to represent malignant lesions and ratios < 1.5 were considered to represent benign lesions. Biopsy revealed four cases of lymphoma, four cases of toxoplasmosis and two cases of progressive multi-focal leukoencephalopathy; one biopsy yielded necrosis. Both the MIBI and 201Tl studies yielded no false-negative cases of lymphoma (sensitivity 100%). Of the 13 non-lymphoma cases, the 201Tl studies showed seven true-negative cases (specificity 54%) and the MIBI studies showed nine true-negative cases (specificity 69%). The biopsies of the false-positive cases (toxoplasmosis) showed a pattern of healing after medical treatment. We conclude that MIBI is more helpful than 201Tl because of higher specificity and equal sensitivity. The medical treatment of toxoplasmosis is a cause of false-positive 201Tl and MIBI studies.

AIDS-Related Opportunistic Infections↗