Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device

<p>Abstract</p> <p>Background</p> <p>Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature.</p> <p>Results</p> <p>A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex.</p> <p>Conclusions</p> <p>A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non-invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation.</p> <p>Background</p> <p>The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood <abbrgrp><abbr bid="B3">3</abbr><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr></abbrgrp>. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) <abbrgrp><abbr bid="B6">6</abbr><abbr bid="B7">7</abbr></abbrgrp>, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology <abbrgrp><abbr bid="B8">8</abbr><abbr bid="B9">9</abbr><abbr bid="B10">10</abbr></abbrgrp>, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>.</p> <p>Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain <abbrgrp><abbr bid="B11">11</abbr></abbrgrp>. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.</p> <p>In the past few years several studies used fMRI to investigate the human trigeminal system <abbrgrp><abbr bid="B12">12</abbr><abbr bid="B13">13</abbr></abbrgrp>, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation <abbrgrp><abbr bid="B14">14</abbr></abbrgrp> or only teeth <abbrgrp><abbr bid="B15">15</abbr><abbr bid="B16">16</abbr><abbr bid="B17">17</abbr></abbrgrp>. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner <abbrgrp><abbr bid="B17">17</abbr><abbr bid="B18">18</abbr></abbrgrp>: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli <abbrgrp><abbr bid="B19">19</abbr></abbrgrp>, as reliability/reproducibility is a necessary feature of sensory testing <abbrgrp><abbr bid="B20">20</abbr></abbrgrp>.</p> <p>Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.</p

Effect of an extract of Centella asiatica on the biodistribution of sodium pertechnetate (Na^99mTcO₄) and on the fixation of radioactivity on blood constituents

This study evaluates the effects of an acute treatment with a Centella asiatica (CA) extract on the biodistribution of the radiopharmaceutical Na99mTcO4 and on the fixation of technetium-99m on blood constituents. Wistar rats were treated with CA extract and, 1 hour after, Na99mTcO4 was administered; organs/tissues were withdrawn and weighted. The radioactivity was counted to calculate the percentage of activity per gram (%ATI/g). Also, blood samples were withdrawn, plasma (P), blood cells (BC), insoluble fraction (IF) and soluble fractions of P and BC were isolated and the radioactivity was counted to calculate the percentage of activity (%ATI). Data indicated that the acute treatment with CA extract changed significantly (p99mTcO4 and the fixation of the technetium-99m on blood constituents in an acute treatment

Nuclear medicine procedures and the evaluation of male sexual organs: a short review

Sexuality consists of three aspects that are interrelated and inseparable, biological, physiological and social. The biological aspect considers the individual's capability to give and to receive pleasure. In consequence, it covers the functionality of the sexual organs and the physiology of human sexual response cycle. Diagnostic imaging modalities, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have been used to evaluate clinical disorders of the male reproductive system. PET and SPECT procedures basically involve the administration of a radiopharmaceutical that has a higher uptake in a specific tumor or tissue. The aim of this brief review is to present some radiopharmaceuticals that have been used in the clinical evaluation of the male sexual organs (testes, prostate, seminal vesicles, penis) related with male sexuality. This information could be useful in better understanding the male sexual response cycle, as well as the sexual disorders, when considering the male sexual organs and the pelvic floor. Moreover, the findings obtained with PET and SPECT imaging could help to evaluate the efficacy of clinical results of therapeutic procedures. In conclusion, the knowledge from these images could aid in better understanding the physiology of the different organs related with sexuality. Furthermore, they could be important tools to evaluate the physiological integrity of the involved organs, to improve clinical strategies and to accompany the patients under treatment

Correlation between voxel based morphometry and manual volumetry in magnetic resonance images of the human brain

This is a comparative study between manual volumetry (MV) and voxel based morphometry (VBM) as methods of evaluating the volume of brain structures in magnetic resonance images. The volumes of the hippocampus and the amygdala of 16 panic disorder patients and 16 healthy controls measured through MV were correlated with the volumes of gray matter estimated by optimized modulated VBM. The chosen structures are composed almost exclusively of gray matter. Using a 4 mm Gaussian filter, statistically significant clusters were found bilaterally in the hippocampus and in the right amygdala in the statistical parametric map correlating with the respective manual volume. With the conventional 12 mm filter,a significant correlation was found only for the right hippocampus. Therefore,narrowfilters increase the sensitivity of the correlation procedure, especially when small brain structures are analyzed. The two techniques seem to consistently measure structural volume.Trata-se de estudo comparativo entre a volumetria manual(VM) e a morfometria baseada no vóxel (MBV), como métodos de avaliação do volume de estruturas cerebrais. Os volumes do hipocampo e da amídala de 16 pacientes de pânico e 16 controles sadios medidos através da VM foram correlacionados com os volumes de matéria cinzenta estimados pela MBV.As estruturas escolhidas são constituídas quase exclusivamente de matéria cinzenta. Utilizando um filtro Gaussiano de 4 mm, encontram-se, bilateralmente, aglomerados significativos de correlação nas duas estruturas no mapa estatístico paramétrico, correspondendo ao respectivo volume manual. Com o filtro convencional de 12 mm, apenas uma correlação significativa foi encontrada no hipocampo direito. Portanto, filtros estreitos aumentam a sensibilidade do procedimento de correlação,especialmente quando estruturas pequenas são analisadas. Ambas as técnicas parecem medir consistentemente o volume estrutural.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)(FAEPA) Hospital das Clínicas da FMRPUSP - Fundação de Apoio ao Ensino, Pesquisa e Asssistênci

Effect of antibodies to intercellular adhesion molecule type 1 on the protection of distant organs during reperfusion syndrome in rats

We investigated kidney and lung alterations caused by intercellular adhesion molecule type 1 (ICAM-1) blockade after ischemia and reperfusion of hind limb skeletal muscles. Rats were submitted to ligature of the infrarenal aorta for 6 h. The animals were randomized into three groups of 6 rats each: group I, sacrificed after ischemia; group II, reperfusion for 24 h, and group III, reperfusion for 24 h after receiving monoclonal anti-ICAM-1 antibodies. At the end of the experiment, blood samples were collected for creatinine, lactate dehydrogenase, creatine phosphokinase, potassium, pH and leukocyte counts. Samples were taken from the muscles of the hind limbs and from the kidneys and lungs for histological analysis and measurement of the neutrophil infiltrate by myeloperoxidase staining. The groups did not differ significantly with regard to the laboratory tests. There were no major histological alterations in the kidneys. An intense neutrophil infiltrate in the lungs, similar in all groups, was detected. Myeloperoxidase determination showed that after reperfusion there was significantly less retention of polymorphonuclear neutrophils in the muscles (352 ± 70 vs 1451 ± 235 × 10² neutrophils/mg; P<0.01) and in the kidneys (526 ± 89 vs 852 ± 73 × 10² neutrophils/mg; P<0.01) of the animals that received anti-ICAM-1 before perfusion compared to the group that did not. The use of anti-ICAM-1 antibodies in this experimental model minimized neutrophil influx, thus reducing the inflammatory process, in the muscles and kidneys after ischemia and reperfusion of the hind limbs.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de CirurgiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de ClínicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUNIFESP, EPM, Depto. de CirurgiaUNIFESP, EPM, Depto. de ClínicaUNIFESP, EPM, Depto. de PatologiaSciEL

Estudo duplo-cego, randômico comparando indinavir, zidovudina e indinavir mais zidovudina na terapia anti-retroviral de indivíduos HIV+ sem tratamento anterior, com contagem de células CD4 entre 50 e 250/mm3

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p&lt;0.0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.Foi demonstrado que o tratamento com indinavir resulta em importante redução da carga viral e aumentos das células CD4 em pacientes infectados pelo HIV. Foi realizado um estudo duplo-cego, randômico para avaliar a eficácia do indinavir isoladamente (800 mg cada 8h), zidovudina isoladamente (200 mg cada 8h) ou a combinação, para avaliar a progressão para AIDS. Foram distribuidos para tratamento 996 pacientes virgens de tratamento antiretroviral, com contagens de CD4 entre 50 e 250 células/mm3. Durante o estudo, o protocolo foi modificado para adicionar lamivudina aos braços contendo zidovudina. O "endpoint" primário foi o tempo para o desenvolvimento de uma doença-definidora de AIDS ou morte. O estudo foi interrompido após uma análise preliminar definida no protocolo ter demonstrado reduções significativas na progressão para um evento clínico nos grupos contendo indinavir, comparado ao grupo da zidovudina (p&lt; 0,0001). Após uma mediana de seguimento de 52 semanas (chegando a 99 semanas), as reduções percentuais nas ocorrências para indinavir+zidovudina e indinavir, comparado com zidovudina foram de 70% e 61%, respectivamente. Reduções significativas na medida do RNA viral e aumentos nas contagens de CD4 também foram observadas nos grupos contendo indinavir, em relação ao da zidovudina. A melhora nas células CD4 e RNA viral foram ambas associadas a risco reduzido de progressão da doença. Os três tratamentos foram geralmente bem tolerados