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Chio A.,University of Turin | Pagani M.,CNR Institute of Neuroscience | Pagani M.,Karolinska University Hospital | Agosta F.,Vita-Salute San Raffaele University | And 4 more authors.
The Lancet Neurology | Year: 2014

In the past two decades, structural and functional neuroimaging findings have greatly modified longstanding notions regarding the pathophysiology of amyotrophic lateral sclerosis (ALS). Neuroimaging studies have shown that anatomical and functional lesions spread beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. Both MRI and PET studies have shown early and diffuse loss of inhibitory cortical interneurons in the motor cortex (increased levels of functional connectivity and loss of GABAergic neurons, respectively) and diffuse gliosis in white-matter tracts. In ALS endophenotypes, neuroimaging has also shown a diverse spreading of lesions and a dissimilar impairment of functional and structural connections. A possible role of PET in the diagnosis of ALS has recently been proposed. However, most neuroimaging studies have pitfalls, such as a small number and poor clinical characterisation of patients, absence of adequate controls, and scarcity of longitudinal assessments. Studies involving international collaborations, standardised assessments, and large patient cohorts will overcome these shortcomings and provide further insight into the pathogenesis of ALS. © 2014 Elsevier Ltd.

Kuzawa C.W.,Northwestern University | Chugani H.T.,Positron | Chugani H.T.,Wayne State University | Grossman L.I.,Wayne State University | And 8 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr%and glucoseder%). We find that glucosermr%and glucoseder%do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr%and glucoseder%are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

Toyohara J.,Positron | Sakata M.,Positron | Ishiwata K.,Positron
Nuclear Medicine and Biology | Year: 2012

Introduction: Carbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([11C]SA4503) was shown to be a promising PET ligand for mapping σ1 receptors, and was applied to human subjects. However, an in vitro study indicated that SA4503 also binds to the emopamil binding protein (EBP), vertebral δ8-δ7 sterol isomerase. To our knowledge, no information is available about the possibility of [11C]SA4503 binding to EBP in the brain in vivo. Methods: To confirm the selectivity of [11C]SA4503, we carried out an in vivo blocking experiment using high-affinity EBP and σ1 selective blocker. Results: The brain uptake of [11C]SA4503 was dose-dependently decreased by SA4503 and the high-affinity σ1 blockers haloperidol, ifenprodil, and trifluperidol. On the other hand, the effects of the high-affinity EBP blockers tamoxifen and trifluoperazine were negligible. Conclusions: Our results confirmed the σ1-selective binding of [11C]SA4503 in the brain. © 2012 Elsevier Inc.

Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. The prevalence of ETT is approximately one per 100,000 to 300,000 persons and is reported to occur in one in 4,000 to 8,000 patients with thyroid disease. Multiple ectopia of thyroid is extremely rare. Multiple ectopia in the presence of orthotopic thyroid gland is extremely rare. We report a 13-year-old boy with stunted growth and developmental delay caused due to acquired hypothyroidism. Technetium scan performed as per management protocol identified dual ectopia of thyroid. The role of hybrid Single-Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) in the localization of the sites of ETT is also highlighted.

Guerard F.,NCI Inc | Lee Y.-S.,U.S. National Institutes of Health | Tripier R.,CNRS Chemistry Laboratory | Szajek L.P.,Positron | And 2 more authors.
Chemical Communications | Year: 2013

Single crystal X-ray diffraction shows that Zr(iv) forms an octa-coordinated complex with 4 bidentate hydroxamates whose solution structures were investigated by utilizing density functional theory at the level of B3LYP/DGDZVP. Stability constants obtained by potentiometry were in accordance with the tendency observed when radiolabeling with 89Zr. © The Royal Society of Chemistry 2013.

Penile cancer is rare cancer. While inguinal and pelvic nodal metastasis is common, distant metastasis is rare. We here present the interesting case of a 59-year-old male patient with penile carcinoma, previously treated with penectomy and inguinal lymphadenectomy 10 years earlier. He presented with bone pains and given history of malignancy he was referred for an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). PET/CT demonstrated multiple 18F-FDG avid bone and lung metastases. No locoregional disease was seen. Biopsy from a lung nodule confirmed the diagnosis, and the patient was started on palliative chemotherapy. © 2016 Indian Journal of Nuclear Medicine | Published by Wolters Kluwer - Medknow.

Smith J.F.,U.S. National Institutes of Health | Pillai A.,U.S. National Institutes of Health | Chen K.,Arizona State University | Chen K.,Positron | Horwitz B.,U.S. National Institutes of Health
NeuroImage | Year: 2010

Dynamic connectivity networks identify directed interregional interactions between modeled brain regions in neuroimaging. However, problems arise when the regions involved in a task and their interconnections are not fully known a priori. Objective measures of model adequacy are necessary to validate such models. We present a connectivity formalism, the Switching Linear Dynamic System (SLDS), that is capable of identifying both Granger-Geweke and instantaneous connectivity that vary according to experimental conditions. SLDS explicitly models the task condition as a Markov random variable. The series of task conditions can be estimated from new data given an identified model providing a means to validate connectivity patterns. We use SLDS to model functional magnetic resonance imaging data from five regions during a finger alternation task. Using interregional connectivity alone, the identified model predicted the task condition vector from a different subject with a different task ordering with high accuracy. In addition, important regions excluded from a model can be identified by augmenting the model state space. A motor task model excluding primary motor cortices was augmented with a new neural state constrained by its connectivity with the included regions. The augmented variable time series, convolved with a hemodynamic kernel, was compared to all brain voxels. The right primary motor cortex was identified as the best region to add to the model. Our results suggest that the SLDS model framework is an effective means to address several problems with modeling connectivity including measuring overall model adequacy and identifying important regions missing from models. © 2009.

Positron emission tomography, most commonly with 18F-fluorodeoxyglucose, is being used for evaluation of tumour response to therapy. Limitations of this method are associated with (1) fluorodeoxyglucose pharmacokinetic properties, (2) the detection system, (3) discrepancies between metabolic and anatomic images, and (4) acquisition standardization. Response to therapy may be evaluated with qualitative (Deauville score), semiquantitative (standardised uptake value), and quantitative methods (European Organization for Research and Treatment of Cancer; Positron Emission Tomography Response Criteria in Solid Tumours). Methods under evaluation include metabolic tumour volume, total lesion glycolysis, and heterogeneity of fluorodeoxyglucose uptake. The development of positron emission tomography scanners that have larger fields of view may facilitate tumour assessment based on kinetic modelling. Increased clinical use of these methods will depend on the development and validation of intuitive and simple analytic tools. © 2014, The Author(s).

An attenuation correction method and device for an image in a PET system. The method includes: acquiring transmission scanning sinogram data from a PET apparatus; reconstructing the transmission scanning sinogram data with Bayesian model-based Ordered Subset Expectation Maximization (OSEM-B) algorithm and Filtered Back Projection (FBP) algorithm, to obtain an OSEM-B attenuation image and a first FBP attenuation image respectively; performing a weighted calculation on the OSEM-B attenuation image and the first FBP attenuation image to obtain an effective attenuation image; and performing attenuation correction on emission scanning sinogram data from the PET apparatus by using an attenuation sinogram generated based on the effective attenuation image.

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