[Magnetic resonance urography in children].
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Adolescent↗
Biomedical subjects
I Gardin
Publications and source records attributed to I Gardin.
Validation of the Monte Carlo simulator GATE for indium-111 imaging.
Monte Carlo simulations are useful for optimizing and assessing single photon emission computed tomography (SPECT) protocols, especially when aiming at measuring quantitative parameters from SPECT images. Before Monte Carlo simulated data can be trusted, the simulation model must be validated. The purpose of this work was to validate the use of GATE, a new Monte Carlo simulation platform based on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of foremost importance for dosimetric studies. To that end, acquisitions of (111)In line sources in air and in water and of a cylindrical phantom were performed, together with the corresponding simulations. The simulation model included Monte Carlo modelling of the camera collimator and of a back-compartment accounting for photomultiplier tubes and associated electronics. Energy spectra, spatial resolution, sensitivity values, images and count profiles obtained for experimental and simulated data were compared. An excellent agreement was found between experimental and simulated energy spectra. For source-to-collimator distances varying from 0 to 20 cm, simulated and experimental spatial resolution differed by less than 2% in air, while the simulated sensitivity values were within 4% of the experimental values. The simulation of the cylindrical phantom closely reproduced the experimental data. These results suggest that GATE enables accurate simulation of (111)In SPECT acquisitions.
Algorithms↗
Impact of Wiener filter in determining the left ventricular volume and ejection fraction using thallium-201 gated SPECT.
Patient morphology, as well as the acquisition and reconstruction parameters, may influence the evaluation of the left ventricular volume (LVV) and left ventricular ejection fraction (LVEF) using gated single-photon emission computed tomography (SPECT). The purpose of this study was to examine the influence of gender and reconstruction filter on the measurement of LVV and LVEF using 201Tl gated SPECT. Using a static torso phantom, a female shape was created by the addition of two saline solution-filled balloons fixed on the anterior rib cage. The following parameters were similar for all acquisitions: 90 degrees dual-head gamma camera; 32 projections; 64x64 matrix (pixel size=6.77x6.77 mm); two 20% energy windows centred at 70 and 167 keV. The following acquisition times were tested: 1.25, 10, 20, 30 and 40 s per projection, leading to a total of 10 successive acquisitions. The effect of over-sampling was tested by 2.5 post-acquisition zooming. All SPECT images were successively reconstructed using filtered back-projection with Butterworth and Wiener filters. The effect of gender and reconstruction filter was also studied in 30 patients (15 males and 15 females) with a low likelihood of coronary artery disease. LVVs were calculated using QGS software. By multivariate analysis, the following factors influenced the accuracy of phantom measurement using QGS software: zooming (F=49, P<0.0001), phantom shape (F=61, P<0.0001) and filter type (F=240, P<0.0001). LVV was underestimated in the female shape phantom, even when using the Wiener filter. In patients, LVV and LVEF measurements were independently influenced by gender (P<0.0001) and filter (P<0.0001), but not by zooming. In conclusion, it was demonstrated that LVV was significantly decreased in the female shape phantom, suggesting a significant impact of breast interposition. This underestimation was minimized by use of the Wiener filter. In patients, the impact of the Wiener filter on the assessment of LVVs and LVEF was powerful, but independent of gender, and failed to correct the underestimation of LVVs and the overestimation of LVEF in females.
Algorithms↗
Comparison of cytogenetic damage in cultured cells from cobalt-60 gamma-radiation and the Auger emitter zinc-65.
PURPOSE: To assess the ability of the Auger-emitting nuclide, zinc-65 (65Zn), relative to gamma-irradiation, to cause chromosomal aberrations in cultured rat prostate cells. MATERIALS AND METHODS: Rat prostate adenocarcinoma cells in culture were exposed to doses of 1, 2, 3 or 5 Gy of external gamma-irradiation for 24h or incubated with 0.7, 1.5, 1.8 or 2.8 MBq of 65Zn for 24 h. The uptake by and clearance from cells of 65Zn was measured. Metaphase spreads prepared from washed cells were scored for chromatid- and chromosome-type aberrations. RESULTS: Following exposure to 65Zn or gamma-irradiation, chromatid-type damage was more commonly observed than chromosome-type aberrations. The relationship between induced chromatid damage and gamma dose (to 3 Gy) was best fitted by a second-order polynomial function, while the activity response relationship for chromatid damage caused by 65Zn appeared to be best fitted by a straight line. Measurements of the uptake of 65Zn by cells showed that average concentrations within cells were about 100 times the concentration in the culture medium. Assuming uniform distribution of 65Zn within cells, with 36% in the nucleus, the dose was estimated as 0.70 Gy per MBq added 65Zn, with Auger electrons contributing most (93%) of the dose. Assuming that 20% of cellular zinc was localized in the nucleus, based on previous measurements, the dose to the nucleus was calculated as 0.44 Gy per MBq added 65Zn. RBE values for chromatid damage induced by 65Zn compared to gamma-radiation range from about 1 to 3 based on a uniform dose throughout the cell and from about 2 to 5 based on 20% of 65Zn in the cell nucleus. CONCLUSION: The observed radiotoxicity of 65Zn is consistent with its behaviour as an Auger-emitting radionuclide that is localized to some extent in the nucleus.
Adenocarcinoma↗
Regulation of FOS by different compartmental stresses induced by low levels of ionizing radiation.
We irradiated different cellular compartments and measured changes in expression of the FOS gene at the mRNA and protein levels. [(3)H]Thymidine and tritiated water were used to irradiate the nucleus and the whole cell, respectively. (125)I-Concanavalin A binding was used to irradiate the cell membrane differentially. Changes in FOS mRNA and protein levels were measured using semi-quantitative RT-PCR and SDS-PAGE Western blotting, respectively. Irradiation of the nucleus or the whole cell at a dose rate of 0.075 Gy/h caused no change in the level of FOS mRNA expression, but modestly (1.5-fold) induced FOS protein after 0.5 h. Irradiation of the nucleus at a dose rate of 0.43 Gy/h induced FOS mRNA by 1.5-fold after 0.5 h, but there was no significant effect after whole-cell irradiation. FOS protein was transiently induced 2.5-fold above control levels 0.5 h after a 0. 43-Gy/h exposure of the nucleus or the whole cell. Irradiation of the cell membrane at a dose rate of 1.8 Gy/h for up to 2 h caused no change in the levels of expression of FOS mRNA or protein, but a dose rate of 6.8 Gy/h transiently increased the level of FOS mRNA 3-fold after 0.5 h. These data demonstrate the complexity of the cellular response to radiation-induced damage at low doses. The lack of quantitative agreement between the transcript and protein levels for FOS suggests a role for post-transcriptional regulation.
Cell Membrane↗
Cell irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences.
Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings. Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.
Humans↗
Use of subtraction ictal SPECT co-registered to MRI for optimizing the localization of seizure foci in children.
UNLABELLED: Ictal SPECT studies are increasingly used to localize seizure foci in children with refractory epilepsy, but few studies have reported on ictal-interictal subtraction images co-registered to MRI at this age. METHODS: Twenty-seven children with partial epilepsy (aged 3 mo-18 y) underwent ictal ethyl cysteinate dimer (ECD) SPECT (20 mCi/1.73 m2) combined with video-electroencephalography (EEG) and interictal ECD SPECT followed 2 d later by three-dimensional MRI. Ictal-interictal and interictal-ictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to each child's MRI. Difference images (ictal-interictal) were then superimposed on MRI for anatomic localization of the perfusion changes. Intra- and interobserver reproducibility and "facility of interpretation" of overlay images were compared with standard analysis of the non-coregistered ictal and interictal scans. RESULTS: Overlay images allowed the detection of at least one hyperperfused focus in 93% of the children, compared with 74% using ictal and interictal scans separately. Seizure onset was suspected clinically, on EEG or on MRI in 20 children. Overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 18 of 20 (90%), whereas these images failed to show any abnormality in 1 child and were discordant with MRI in another patient. In the remaining 7, images showed cortical localization in 6 patients. Among the 5 patients who underwent electrocorticography, overlay images were concordant in 3, larger in 1 and absent in 1. The intra- and interobserver reproducibility and facility of interpretation were significantly higher using overlay images than standard analysis, even when ictal and interictal SPECT were co-registered. CONCLUSION: The co-registration of ictal-interictal subtraction SPECT images to MRI seems to be a helpful technique in localizing the onset of seizure and guiding the intracranial recording in childhood epilepsy. Moreover, this method improves sensitivity, enhances intra- and interobserver reproducibility and makes interpretation easier.
Adolescent↗
[Ictal SPECT in the epileptic child. Contribution of subtraction interictal images and superposition of with MRI].
Ictal SPECT is a highly sensitive method to localize the epileptogenic focus in refractory temporal lobe epilepsy in adults. In extratemporal epilepsy, sensitivity can be improved by subtracting interictal from ictal images and superimposing subtraction images on MRI. In children, such a procedure is potentially interesting because most epilepsies are extratemporal and ictal SPECT not yet routinely developed. The aim of this study was to test the feasibility of ictal SPECT with subtraction image processing in a pediatric population. Twenty-six children with refractory partial epilepsy and aged from 3 months to 18 years underwent ictal ECD-SPECT (20 mCi/1.73 m2) combined with video-EEG and interictal ECD-SPECT plus 3D-MRI two days later. Ictal-interictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to the children's MRI. Difference images were then superimposed to MRI for anatomical localization of the perfusion changes (overlay images). Looking for perfusion changes, overlay images allowed to detect at least one hyperperfused focus in 92 p. 100 of the 26 children compared to 73 p. 100 visually comparing ictal and interictal scans separately. Seizure onset was suspected on clinical and/or EEG and/or MRI in 19 children. Positive overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 17/19 (90 p. 100), whereas they failed to show any abnormality in 1 child and were discordant with MRI in another one. In the 7 remaining patients, images showed cortical localization in 6 cases. Ictal SPECT is therefore faisable in very young children. Ictal-interictal subtraction SPECT images co-registered to MRI improves sensitivity compared to classical visual analysis. It seems therefore to be a helpful technique to localize the onset of seizure and to guide the intracranial recording in childhood epilepsy.
Adolescent↗
Comparison of cellular and conventional dosimetry in assessing self-dose and cross-dose delivered to the cell nucleus by electron emissions of 99mTC, 123I, 111In, 67Ga and 201T1.
The radionuclides used in nuclear medicine imaging emit numerous mono-energetic electrons responsible for dose heterogeneity at the cellular level. S(self) the self-dose per unit cumulated activity (which results from the radionuclide located in the target cell), and S(cross) the cross-dose per unit cumulated activity (which comes from the surrounding cells) delivered to a target cell nucleus by electron emissions of technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201 were computed at the cellular level. An unbounded close-packed hexagonal cell arrangement was assumed, with the same amount of radioactivity per cell. Various cell sizes and subcellular distributions of radioactivity (nucleus, cytoplasm and cell membrane) were simulated. The results were compared with those obtained using conventional dosimetry. S(self) and S(cross) values depended closely on cell dimensions. While the self-dose depended on the tracer distribution, the latter affected the cross dose by less than 5%. When the tracer was on the cell membrane, the self-dose was particularly low compared to the cross-dose, as the self-dose to cross-dose ratio was always less than 11%. In the case of cytoplasmic or cell membrane distribution of radioactivity, conventional electron dosimetry slightly overestimated the dose absorbed by the target cell nucleus (by 1.08-to 1.7-fold). In contrast, conventional dosimetry strongly underestimated the absorbed dose (1.1- to 75-fold) when the radioactivity was located in the nucleus. The discrepancies between conventional and cellular dosimetry call for calculations at the cellular level for a better understanding of the biological effects of radionuclides used in diagnostic imaging.
Algorithms↗
Edge detection in brain SPET perfusion imaging: a comparison of several methods.
Four methods of brain edge detection on brain SPET perfusion (99Tcm-hexamethylpropylene amine oxime) images were compared: ellipse adaptation, simple thresholding (four threshold values), a low threshold (40%) followed by 1, 2 or 3 pixel erosion, and the Deriche 3D adaptive cut-off frequency method (four filter widths: alpha = 1, 2, 3 or 4). The SPET data of six patients were reconstructed to obtain 10 axial slices, each 10 mm thick, covering the whole brain. On the 60 axial slices, the methods were compared based on automaticity, computation time and accuracy of edge detection compared with morphological edges drawn manually on the patients' 3D co-registered magnetic resonance imaging (MRI) scans. The proportion of pixels inside the contour defined by the MRI scan but outside the SPET edge (p(i)), and the proportion of pixels inside the contour defined by the SPET image but outside the MRI contour (pe), were calculated. The thresholding methods provided interesting results, particularly the application of a low threshold value (40%), followed by a 2 pixel erosion, which required a computation time of 12 s (p(i) = 5.7 +/- 2.2%; pe = 2.7 +/- 0.9%). Because of adjustments to each slice of the ellipse axis, the processing time of this method was about 3 min (p(i) = 1.5 +/- 1.4%; pe = 11.3 +/- 3.4%). The Deriche 3D filter was time-consuming (6 min for 10 slices on a NXT workstation, SMV International). With this method, the best edge fitting was found with a filter width of 3 and 4 (p(i) = 9.6 +/- 11.1%; pe = 14.1 +/- 23.2%; alpha = 3). Three-dimensional filtering methods must be refined to reduce the computation time and to improve brain edge fitting accuracy when compared with the eroded thresholding method.
Brain↗
A place for cellular dosimetry in risk assessment.
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Animals↗
Proportional anatomical stereotactic atlas for visual interpretation of brain SPET perfusion images.
A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain single-photon emission tomographic (SPET) perfusion images, and then to draw the proportional anatomical Talairach's grid on each axial SPET image. First, the AC-PC line was defined on SPET images from the linear regression of four internal landmarks (frontal pole of the brain, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPET position of AC and PC points on the AC-PC line was automatically determined from measurements made on hard copies of magnetic resonance (MR) images of the patients. Finally, a proportional Talairach's grid was automatically drawn on each axial SPET image. To assess the accuracy of localization of AC and PC points, co-registered technetium-99m hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used. The mean displacements between estimated points on SPET and true points on MRI (Deltax=sagittal, Deltay=frontal and Deltaz=axial displacement) were calculated. The mean displacements (in mm) were Deltax=-1.4+/-1.8, Deltay=-1.7+/-3.3 and Deltaz=-1. 1+/-2.5 for AC, and Deltax=-1.8+/-1.8, Deltay=0.3+/-3.2 and Deltaz=-1.3+/-2.7 for PC. These displacements represented an error of less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Intra- and inter-observer comparisons did not reveal significant differences in mean displacements. Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPET perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPET-MRI co-registration.
Algorithms↗
Absorbed fraction to the cell nucleus for low energy electrons.
The absorbed fraction phi to the cell nucleus for low energy electrons (0.5 keV-50 keV) was evaluated. Distributions of radioactivity within either the nucleus (nu) and the cytoplasm (cy), or on the cell membrane (mem) were considered. phi was computed as a function of the cell sizes and of the electron energy E. For a strictly intranuclear distribution, phi(nu) is close to 1 for very low energy values (E < 4 keV), i.e. the energy is totally absorbed in the cell nucleus itself. The absorbed fraction decreases when the energy increases and phi(nu) becomes less than 0.1 for E > or = 40 keV. For a cell membrane distribution, the absorbed fraction remains always less than 0.2. For very low energy electrons (E < 6 keV), phi(mem) = 0, due to the fact that the electron falls short to the nucleus target. The absorbed fraction is maximum for E ranging from 12 keV to 20 keV. For higher values of E, phi(mem) decreases when E increases. When considering a cytoplasmic distribution, the maximum absorbed fraction phi(cy) is obtained for E values ranging from 10 keV to 25 keV (phi(cy max) = 0.27). Dosimetric computations at the cellular level show that the absorbed fraction to the cell nucleus may have values ranging from 0 to 1, depending on the dimensions of the cell, the energy of the emitted electron and on the intracellular localization of the Auger emitter.
Absorption↗
Modelling of the relationship between cell dimensions and mean electron dose delivered to the cell nucleus: application to five radionuclides used in nuclear medicine.
The mean dose delivered to the cell nucleus by electron emissions of 99Tcm, 123I, 111In, 67Ga and 201Tl was evaluated at the subcellular level. Models were applied assuming uniform distributions of radioactivity throughout the nucleus, the cytoplasm or the cell membrane, allowing computation of the total absorbed fraction, phi and S-values to the cell nucleus as a function of cell dimensions. The graphs of phi plotted according to cell dimensions show that the dose to the cell nucleus strongly depends on the subcellular distribution of radioactivity, the nucleus radius Rnucl and the cytoplasmic thickness e. For a nuclear distribution, phi ranges from 0.1 to 0.35 for the radionuclides studied and S from 0.049 cGy Bq-1 s-1 to 5.503 cGy Bq-1 s-1. In the case of a cell membrane localization, the maximum is obtained for 123I (phi = 0.016). For a cytoplasmic distribution, the maximum is obtained for 201Tl with a value of 0.036. To ease future calculations, third-degree polynomials have been separately fitted to the relationship between the mean absorbed dose to the nucleus for activity accumulated in the nucleus, cytoplasm or surface of the cell membrane. We found a good agreement between our computations and the values obtained by the polynomials. The relative difference between the two methods is always less than 0.7%, 2.8% and 4.5% respectively for nuclear, cell membrane and cytoplasmic distributions.
Cell Membrane↗
Comparative study of three automatic programs of left ventricular ejection fraction evaluation.
The aim of this study was to compare three automatic programs (P1, P2, P3) for evaluating radionuclide left ventricular ejection fraction (LVEF) and to emphasize the clinical consequences. Gated radionuclide ventriculography was performed in 73 subjects, 15 of whom were healthy and 58 of whom had experienced heart failure. All scintigraphic data were processed with the three programs. Good inter-observer, intra-observer and automatic-manual reproducibility were observed using each of the three programs. On the other hand, in the normal subjects, the three mean normal LVEF values were significantly different from each other (P1 = 77 +/- 5%, P2 = 63 +/- 7%, P3 = 68 +/- 8%; P < 0.0001) In the pathological patients, the values obtained with P2 were significantly different from those obtained using P1 and P3 (P1= 32 +/- 15%, P2 = 26 +/- 13%; P < 0.0001), Moreover, the linear regression studies between the three automatic programs were always significantly different from the identity line equation (y = x). This study shows that LVEF criteria for normality depend on the program used, and inter-program measurement of LVEF is poorly reproducible. Caution is recommended when comparing data obtained from different centres (or different computers), either in the follow-up of a given patient or in gathering results from patient groups.
Adult↗
The influence of tracer localization on the electron dose rate delivered to the cell nucleus.
UNLABELLED: The radiation dose rate delivered by electron emissions of 99mTc, 123I, 111In, 67Ga and 201Tl was evaluated at the subcellular level. METHODS: Spherical models of sources were used to simulate various cellular localizations of radionuclides. These models were applied to large lymphocytes, assuming uniform distributions of radioactivity throughout the nucleus, the cytoplasm or the cell membrane surface. RESULTS: The graphs of the absorbed dose rate plotted according to the distance from the center of the cell show that the dose rate strongly depends on the subcellular distribution of the radioisotope. The absorbed dose rate D(0) at the center of the cell delivered by a constant cellular radioactivity of 99mTc, 123I, 111In, 67Ga and 201Tl is respectively 94, 21, 18, 74 and 76 times higher if the radioactivity is localized within the cell nucleus than if it is situated only on the cell membrane. D(0) for subcellular localizations was compared to D(0) obtained by assuming uniform distribution of radioactivity throughout the cell. This latter assumption may underestimate the dose rate from 2.8- to 3.2-fold if the tracer is exclusively localized within the nucleus or overestimate from 4.3- to 30-fold if the tracer is localized within the cytoplasm or on the cell membrane, depending on the radionuclide. CONCLUSION: Such findings show that the localization of radiopharmaceuticals at the subcellular level plays a crucial role in determining the actual dose delivered to the cell nucleus in diagnostic nuclear medicine procedures.
Cell Membrane↗
Dosimetry at the cellular level of Kupffer cells after technetium-99m-sulphur colloid injection.
The radiation dose to Kupffer cells was estimated at the cellular level after intravenous injection of 99mTc labeled sulphur colloids in rats. The results were then compared with those obtained using macroscopic dosimetry. From the microscopy appearance observed using a "track" microautoradiographic method (MAR), it was shown that only 0.2% of the Kupffer cells were actually involved in the pinocytosis of radioactive colloids. For each electronic emission from 99mTc (Auger and internal conversion), the fraction of the emitted energy actually absorbed within the Kupffer cell was calculated using the values provided by Berger. About 15% of the total energy emitted by electrons was absorbed in 0.2% of the Kupffer cells. If these results are extrapolated to humans, the dose absorbed by the labeled cells can be estimated to be between 0.5 and 0.9 Gy/MBq. This represents about 15,000 times the average electron dose to the liver as estimated from macrodosimetric methods. In cases such as this one where an important distribution heterogeneity is expected, dosimetric estimations at a cellular level may be particularly useful.
Animals↗
Pharmacokinetics and tissue distribution of 99mTc-labelled enoxaparin in the rat: evaluation of dosimetry parameters.
A low molecular weight heparin, enoxaparin, was labelled with 99mTc and the characteristics of the labelled compound determined. In vitro the stability, and labelling efficiency (98%) of the labelled drug were excellent. Rats were injected with 99mTc-enoxaparin to study pharmacokinetics and distribution. The results were used to calculate dosimetric estimates which are a prerequisite for pharmacokinetic studies on labelled LMWH (low molecular weight heparin) in human subjects. Biodistribution studies showed preferential liver and spleen accumulation. But the doses absorbed by these target organs remained below the upper limits of the dose received by a patient undergoing hepatic scintigraphy.
Animals↗