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Biomedical subjects

G Placidi

Publications and source records attributed to G Placidi.

14 recordsLinked to original sources

Child thyroid disruption by environmental chemicals.

Laboratory experiments and animal evidences support the fact that thyroid function can be altered by a large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. Although humans are commonly exposed to low pollutant doses, disrupting effects on endocrine function (e.g. thyroid) from such chemical exposures represent major health concerns. Thyroid is essential for mammalian brain development both before and after birth, and recent clinical evidences strongly suggest that brain development is much more sensitive to thyroid hormone excess or deficit than previously believed. Thyroid hormone deficit or excess during development can have permanent, pervasive and profound effects on the neurological function of the child. In addiction, maternal thyroid hormones play a role in fetal brain development before the onset of fetal thyroid function, and thyroid hormone deficit in pregnant women can produce irreversible neurological effects in their offspring. Considering that thyroid hormones are important in fetal brain development and child neurological outcome, environmental factors affecting maternal/fetal/infant thyroid function, or thyroid hormone action directly, may affect fetal brain development and child neurological outcome. The aim of this paper is to discuss how environmental chemicals can interfere with the normal production, metabolism, and excretion of thyroid hormones, and their known impact on the thyroid system during child development.

Brain↗

Versatile coil design and positioning of transverse-field RF surface coils for clinical 1.5-T MRI applications.

Clinical MRI/MRS applications require radio frequency (RF) surface coils positioned at an arbitrary angle alpha with respect to B(0). In these experimental conditions the standard circular loop (CL) coil, producing an axial RF field, shows a large signal loss in the central region of interest (ROI). We demonstrate that transverse-field figure-of-eight (FO8) RF surface coils design are not subject to the same amount of signal loss in the central ROI as loop coils when their orientations are changed. The 1.5-T CL and FO8 prototypes (diameter = 10 cm) were built on Plexiglas using copper strips (width = 4 mm, thickness = 100 mum). The two linear elements of the FO8 coil were 1 cm apart. Axial spoiled gradient echo (SPGR) images of a phantom containing doped water were acquired with the coil plane at alpha=0 degrees , 45 degrees , and 90 degrees . As alpha increases, the CL images show, in the central ROI, a signal that decreases from a maximum value to zero. Whereas the FO8 images show, in the same ROI, a signal that varies little from the maximum value (20%). Optimized FO8 coils can be oriented with the coil plane positioned along any direction with respect to B(0) without significant signal loss. Transverse RF coil design should be useful for clinical MRS studies and also for parallel imaging techniques where versatile RF coils disposed along arbitrary directions are required.

Computer Simulation↗

New experimental apparatus for multimodal resonance imaging: initial EPRI and NMRI experimental results.

Electron paramagnetic resonance imaging (EPRI) is a recently developed imaging technique employed in the study of free radicals in living systems. A full understanding of many physiological and pathological processes involving free radicals has not yet been attempted. The reason for this is that whilst nuclear magnetic resonance imaging (NMRI) is able to generate very accurate images of soft tissues and organs, EPRI does not have this capability because of its sensitivity limitations and the large linewidths of paramagnetic probes. This work describes the development and optimization of a multimodal apparatus capable of performing both pulsed EPRI and NMRI experiments on the same sample. The instrument combines the possibilities offered by both techniques: the functional and biochemical information achieved with EPRI, and the high-resolution anatomical images generated by NMRI. At present, these experiments are performed by moving the sample from an EPRI spectrometer to an NMRI apparatus. Consequently, the acquisition times are very long and several problems arise in image reconstruction. On the other hand, a unique apparatus operating in the two modalities greatly reduces the acquisition times and makes it possible to relate accurately the observed distribution of electron spin density with the anatomical description of individual organs. The experiments are performed at 357 Gauss, corresponding to a resonance frequency of 1.52 MHz for NMR and 1 GHz for EPR. In the present work, a detailed description of the apparatus is reported, including the main magnet, the gradient assembly, the multimodal cavity and the transmitter and receiver systems. The preliminary experimental results obtained by this apparatus are presented.

Electron Spin Resonance Spectroscopy↗

Omega-space adaptive acquisition technique for magnetic resonance imaging from projections.

An omega-space adaptive acquisition technique for MRI from projections is presented. It is based on the evaluation of the information content of a set composed of four initial projections, measured at angles 0 degrees, 45 degrees, 90 degrees, and 135 degrees, followed by the selection of new angles where the information content is maximum. An entropy function is defined on the power spectrum of the projections that is useful for evaluating the information content of each projection. The method makes it possible to reduce the total acquisition time with little degradation of the reconstructed image and it adapts to the arbitrary shape of the sample. For this reason, it can be particularly useful in those applications where acquisition from projections is strongly recommended to save acquisition time, such as functional MRI, imaging of species having very short T(2), or angiography. The method has been tested both on simulated data and on experimental data collected by a commercial MRI apparatus. The method has also been compared to the regular acquisition method, that is, the standard acquisition method in MRI from projections.

Image Processing, Computer-Assisted↗

EPR imaging from projections: errors due to misalignment of projection centres and their rectification by a novel acquisition modality.

Continuous wave and pulsed wave electron paramagnetic resonance imaging (EPRI) makes use of classical methods of acquisition of projections. Acquisition/reconstruction techniques, such as spin-echo, gradient-echo, etc, cannot be applied to EPRI because they would require very short switching times for the gradient coils. Due to the use of the polar acquisition technique, it is necessary to define a centre of rotation about which the measured projections are rotated during the reconstruction process. This centre represents the point at which the field gradient coils must produce zero magnetic field. Due to the presence of a magnetic field control system that serves to compensate for field variations, principally due to heating, some interference can occur in the control system between the main magnetic field and the magnetic field produced by the gradient coils. The effect changes as the orientation changes. This results in a shift of the centres of the projections as a function of the variation of magnetic field produced by the gradient coils on the control Hall probe. If this condition is present, some artefacts can appear on the reconstructed image. This effect is irrelevant when EPR is used for imaging of paramagnetic probes whose linewidths are of the order of 10(-4) T, while it can be significant in the case of linewidths of the order of 10(-5) T or lower or when EPR is used in microimaging applications (i.e. for high values of magnetic field gradient). We describe the effects that misalignments of the projections have on the reconstructed images. We present a useful method for estimating the real position of the centre and correcting the measured projections before the application of the reconstruction algorithm. Moreover, we demonstrate the functioning of our technique by presenting some examples of EPR reconstruction collected by an X-band EPR imaging apparatus.

Algorithms↗

Pulsed EPR imaging: image reconstruction using selective acquisition sequences.

Pulsed nuclear magnetic resonance imaging (NMRI) apparatus has developed very quickly. On the other hand, the development of apparatus for pulsed electron paramagnetic resonance imaging (EPRI) has been very slow. This fact is due to the extremely reduced relaxation times of the paramagnetic probes. EPR linewidths are larger than typical NMR linewidths. These large linewidths are also responsible for a substantial worsening of spatial resolution. Due to the brevity of the electronic relaxation times, not all the acquisition/reconstruction techniques currently used in NMRI (such as spin-echo, gradient-echo, etc) can be applied in pulsed EPRI. In fact, the usable sequences in pulsed EPRI are only acquisitions from projections, where it is possible to use stationary magnetic field gradients. Moreover, the use of high fixed magnetic field gradients induces a short decay time constant T2*. The low T2* value can make it impossible for the analogue to digital conversion system (ADC) to reproduce signal variations during the whole acquisition interval and the resolution can worsen. A new pulsed EPRI acquisition sequence from projections, based on selective reception, is presented that is particularly useful in solving the problems of worsening of spatial resolution associated with the use of an ADC. In order to demonstrate the capabilities of our acquisition method, simulated numerical tests will also be reported.

Electron Spin Resonance Spectroscopy↗

A Radiofrequency (220-MHz) Fourier Transform EPR Spectrometer

Radiofrequency continuous wave EPR spectrometers for detecting and localizing free radicals in vivo in samples of 50-100 g have been developed. The main limitation of these EPR instruments is the slow acquisition time, and a sensible improvement is expected by the adoption of pulsed EPR techniques. We present here a Fourier transform EPR spectrometer operating at 220 MHz suitable for large volume samples (up to 50 ml). A detailed description of the transmitter and receiver sections, including the EPR resonator, is given. Representative free induction decay data obtained from a sample with a relaxation time of about 900 ns are reported. Copyright 1998 Academic Press.

Journal Article↗

Fourier reconstruction as a valid alternative to filtered back projection in iterative applications: implementation of Fourier spectral spatial EPR imaging.

The qualitative equivalence between the Fourier reconstruction (FR) algorithm and the filtered back projection (FBP) algorithm is demonstrated when all the different phase errors that can occur in FR are eliminated. The causes of phase errors are underlined and methods to eliminate them are presented. The practical comparison between FR and FBP has been evaluated on a numerical test image and the results are reported, demonstrating the qualitative equivalence. FR has the advantage of being very computationally efficient. In fact, the time spent to obtain the FR image was 1/20 of that used to obtain the FBP image. Because of the computational efficiency of FR and the good quality of the results obtained, an iterative version of FR has been used to implement the spectral-spatial imaging (SSI) algorithm in the field of electron paramagnetic resonance imaging (EPRI). An experimental example, demonstrating its good performance, is reported.

Electron Spin Resonance Spectroscopy↗

Chronic recurrent stress due to panic disorder does not precipitate Graves' disease.

A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.

Adolescent↗

Two-dimensional 220 MHz Fourier transform EPR imaging.

In the last decade radiofrequency continuous-wave EPR spectrometers have been developed to detect and localize free radicals in vivo. Only recently, pulsed radiofrequency EPR spectrometers have been described for imaging applications with small samples. In the present work, we show the first two-dimensional image obtained at 220 MHz on a large phantom (40 ml) that simulates typical conditions of in vivo EPR imaging. This pulsed EPR apparatus has the potential to make the time required for three-dimensional imaging compatible with the biological half-life of normally used paramagnetic probes.

Animals↗

pH-sensitive imaging by low-frequency EPR: a model study for biological applications.

The use of pH-sensitive nitroxides, in conjunction with low-frequency EPR, offers a unique opportunity for non-invasive assessment of pH values (in the range 0 to 14) in living animals. In the present study, we have investigated the potential use of pH-sensitive nitroxide free radicals in conjunction with EPR imaging techniques at low and very low frequencies (280 MHz-2.1 GHz). In particular, we have measured the hyperfine splitting (hfs) of a pH-sensitive probe at three different EPR frequencies: 280 MHz, 1.1 GHz and 2.1 GHz. We have also developed EPR imaging experiments with phantoms simulating in vivo conditions, using pH-sensitive probes at 280 MHz (spatial-spatial) and 1.1 GHz (spectral-spatial). Finally, we discuss the actual sensitivity/resolution limits of the EPR imaging techniques at low frequencies. Practical applications of this method in the biomedical field are suggested for the continuous and non-invasive localization of pH in vivo.

Animals↗

Water soluble free radicals as biologically responsive agents in electron paramagnetic resonance imaging.

Electron paramagnetic resonance imaging (EPRI) is currently being developed at frequencies between 200 MHz and 2 GHz. EPRI can map the in vivo distribution of paramagnetic species, such as water soluble free radicals; nitroxide free radicals are commonly used. EPR images reflect the complexity of metabolic actions on the exogenous delivered nitroxides. Their reduction rate in vivo is affected by parameters such as oxygen concentration, pH and biodistribution. This paper illustrates the main features of low frequency EPRI and reconstruction techniques. Examples of EPR imaging, such as two-dimensional (2D) spatial mapping of the distribution of a nitroxide free radical in phantoms and in whole rat, are given.

Animals↗

Exploration of the clinical profile of rubidium chloride in depression: a systematic open trial.

Thirty-one female inpatient depressives underwent a systematic open trial with rubidium chloride, 180 to 720 mg/day. By week 2, at least two-thirds had improved significantly (p less than 0.01) as measured by standard rating instruments such as the Brief Psychiatric Rating Scale and the Hamilton Depression Scale. Regression analysis suggested that the retarded endogenous pattern was most predictive of positive response. Treatment-emergent symptomatology, such as diarrhea, polyuria, and excitement, was generally mild and rarely necessitated interruption of the trial. The authors conclude that this salt has shown sufficient clinical promise to warrant more extensive trials under double-blind conditions.

Adult↗

Young Investigator Award presentation at the 13th Annual Meeting of the ESMRMB, September 1996, Prague. A proton-electron double-resonance imaging apparatus with simultaneous multiple electron paramagnetic resonance irradiation at 10 mT.

The detection of free radicals in vivo is very important for the study of many physiologic and pathologic conditions. Free radicals have been implicated in a number of diseases such as ischemia, inflammation, kidney damage, and cancer. Proton-electron double-resonance imaging (PEDRI) allows the indirect detection of free radicals via the Overhauser effect. Nitroxide free radicals used for in vivo PEDRI studies present spectra with two or three lines, but most PEDRI experiments performed to date have used only single-line electron paramagnetic resonance (EPR) irradiation. There is theoretical evidence that simultaneous irradiation of multiple EPR transitions could increase the maximum achievable PEDRI enhancement. From the experimental point of view, this requires the combined use of a suitable multiple-frequency EPR source and a multiple-tuned EPR resonator. A novel radiofrequency (RF) triple-tuned loop-gap resonator for use in PEDRI has recently been developed, and dynamic nuclear polarization (DNP) data were reported. In the present study we describe a new PEDRI apparatus, equipped with a triple-tuned resonator, that is suitable for simultaneous double- or triple-EPR irradiation of nitroxide free radicals. In particular, the details of the EPR hardware used to generate the two or three EPR frequencies are given, and PEDRI images obtained with simultaneous multiple EPR irradiation are shown. Moreover, DNP experimental results showing the increase of the enhancement as a function of the EPR power for single and simultaneous double EPR irradiation are presented. The main goal of this apparatus is to improve the sensitivity and/or to reduce EPR irradiation power in a PEDRI experiment. This is likely to be particularly important in future biologic applications of PEDRI where the applied power must be optimized to reduce sample heating.

Awards and Prizes↗