[en] It has been proposed that increased brain iron is a nonspecific marker of neuropathology and may arise from the interruption of iron transport pathways or directly from cell injury. The purpose of this paper is to derive reliable and quantified standards for brain iron in carefully screened normal subjects and relate these to normal aging, so that pathologic accumulations of iron can be more reliably diagnosed. The patient population consisted of 49 volunteers who were carefully screened by means of extensive risk factor analysis and neuropsychiatric testing. Continguous-section spin-echo MR imaging was performed at 1.5 T (TR, 3,000 msec, TE, 30 and 80 msec). Volume calculations were performed with a previously verified segmentation program based on semiautomatic partitioning of bifeature space

[en] N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β(4-chlorophenyl)tropane (IPT) is an analog of cocaine that selectively binds the presynaptic dopamine transporter. The present study sought to measure the radiation dosimetry of IPT in seven healthy human volunteers. Dynamic renal scans were acquired immediately after the intravenous administration of 165 ± 16 MBq (4.45 ± 0.42 mCi) of [¹²³I]IPT. Between 7 and 12 sets of whole-body scans were acquired over the next 24 hr. The 24-hr renal excretion fractions were measured from conjugate emission scans of 7-11 discreet voided urine specimens. The fraction of the administered dose in 11 organs and each urine specimen was quantified from the attenuation-corrected geometric mean counts in opposing views. Subject-specific residence times were evaluated for each subject independently by fitting the time-activity curves to a multicompartmental model. The radiation doses were estimated with the MIRD technique from the residence times for each subject individually before any results were averaged. The findings showed that IPT was excreted rapidly by the renal system. There were no reservoirs of retained activity outside the basal ganglia, where SPECT images in these subjects showed that the mean ratio of caudate to calcarine cortex averaged 25:1 at 3 hr after injection (range 19.6-32 hr). The basal ganglia received a radiation dose of 0.028 mGy/MBq (0.10 rad/mCi). The dose-limiting organ in men was the stomach, which received an estimated 0.11 mGy/MBq (0.37 rad/mCi). In women, the critical organ was the urinary bladder at 0.14 mGy/MBq (0.51 rad/mCi). Relatively high-contrast images of the presynaptic dopamine transporters in the basal ganglia can be acquired with 185 MBq (5 mCi) of [¹²³I]IPT. The radiation exposure that results is significantly less than the maximum allowed by current safety guidelines for research volunteers. 33 refs., 4 figs., 3 tabs

[en] A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T₂ pixel values to correct field inhomogeneities (shading). Average (±SD) brain volume, excluding cerebellum, was 1090.91 ml and cerebrospinal fluid (DSF) volume was 127.91 ml. Brain volume was higher (by 5 ml) in the right hemisphere. Men had 91 ml higher brain and 20 ml higher CSF volume than women. Age was negatively correlated with brain volume and positively correlated with CSF volume. The slope fo the regression line with age for CSF was steeper for men than women. This difference in slopes was significant for sulca but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas is women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions

[en] The choice of a collimator and the selection of a filter can affect the quality of clinical SPECT images of the brain. The compromises that 4 different collimators make between spatial resolution and sensitivity were studied by imaging a three-dimensional Hoffman brain phantom. The planar data were acquired with each collimator on a three-headed SPECT system and were reconstructed with both a standard Butterworth filter and a Wiener pre-filter. The reconstructed images were then evaluated by specialists in nuclear medicine and were also quantitatively analyzed with specific regions of interest (ROI) in the brain. All observers preferred the Wiener filter reconstructed images regardless of the collimator used to acquire the planar images. With this filter, the ultrahigh-resolution fan-beam collimator was the most subjectively preferable and quantitatively produced the highest contrast ratios. The findings support suggestions that higher resolution collimators are preferable to higher sensitivity collimators, and indicate that fan-beam collimators are preferable to parallel-hole collimators for clinical SPECT studies of cerebral perfusion. The results also suggest that the Wiener filter enhances the quality of SPECT brain images regardless of which collimator is used to acquire the data. (author)

[en] Positron emission tomography (PET) and single-photon emission tomography (SPET) imaging of the dopaminergic system is a powerful tool for distinguishing groups of patients with neurodegenerative disorders, such as Parkinson's disease (PD). However, the differential diagnosis of individual subjects presenting early in the progress of the disease is much more difficult, particularly using region-of-interest analysis where small localized differences between subjects are diluted. In this paper we present a novel pixel-based technique using logistic discriminant analysis to distinguish between a group of PD patients and age-matched healthy controls. Simulated images of an anthropomorphic head phantom were used to test the sensitivity of the technique to striatal lesions of known size. The methodology was applied to real clinical SPET images of binding of technetium-99m labelled TRODAT-1 to dopamine transporters in PD patients (n=42) and age-matched controls (n=23). The discriminant model was trained on a subset (n=17) of patients for whom the diagnosis was unequivocal. Logistic discriminant parametric maps were obtained for all subjects, showing the probability distribution of pixels classified as being consistent with PD. The probability maps were corrected for correlated multiple comparisons assuming an isotropic Gaussian point spread function. Simulated lesion sizes measured by logistic discriminant parametric mapping (LDPM) gave strong correlations with the known data (r²=0.985, P<0.001). LDPM correctly classified all PD patients (sensitivity 100%) and only misclassified one control (specificity 95%). All patients who had equivocal clinical symptoms associated with early onset PD (n=4) were correctly assigned to the patient group. Statistical parametric mapping (SPM) had a sensitivity of only 24% on the same patient group. LDPM is a powerful pixel-based tool for the differential diagnosis of patients with PD and healthy controls. The diagnosis of disease even before clinical symptoms become apparent may be possible, and ultimately this technique could be most useful in differentiating between several neurodegenerative disorders, incorporating images of multiple neuroreceptor systems. (orig.)

[en] A new PET ligand, 3-fluoro-5-(2-(2-¹⁸F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (¹⁸F-SP203), is a positron emission tomographic radioligand selective for metabotropic glutamate subtype 5 receptors. The purposes of this study were to estimate the radiation-absorbed doses of ¹⁸F-SP203 in humans and to determine from the distribution of radioactivity in bone structures with various proportions of bone and red marrow whether ¹⁸F-SP203 undergoes defluorination. Whole-body images were acquired for 5 h after injecting ¹⁸F-SP203 in seven healthy humans. Urine was collected at various time points. Radiation-absorbed doses were estimated by the Medical Internal Radiation Dose scheme. After injecting ¹⁸F-SP203, the two organs with highest radiation exposure were urinary bladder wall and gallbladder wall, consistent with both urinary and fecal excretion. In the skeleton, most of the radioactivity was in bone structures that contain red marrow and not in those without red marrow. Although the dose to red marrow (30.9 μSv/MBq) was unusually high, the effective dose (17.8 μSv/MBq) of ¹⁸F-SP203 was typical of that of other ¹⁸F radiotracers. ¹⁸F-SP203 causes an effective dose in humans typical of several other ¹⁸F radioligands and undergoes little defluorination. (orig.)

[en] Quantification of dopamine transporters (DAT) using [^99mTc]TRODAT-1 and single-photon emission tomography (SPET) requires full kinetic modeling of the data, using complex and invasive arterial blood sampling to provide an input function to the model. We have shown previously that a simpler reference tissue model provides accurate quantitative results, using a reference region devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop further simplifications to make the imaging protocol much more practical as a routine procedure. Fourteen healthy subjects (age 29.8±8.4 years, range 18.7-45.5 years) underwent dynamic SPET for 6 h following injection of 752±28 MBq [^99mTc]TRODAT-1. The kinetic data were analyzed using nonlinear regression analysis (NLRA) and Logan-Patlak graphical analysis. In addition, simple average ratios of striatal-to-background counts were obtained for three 1-h periods (3-4 h, 4-5 h, 5-6 h), and compared against the kinetic models. All methods gave an index of specific binding, proportional to the binding potential, known as the distribution volume ratio (DVR). The reference tissue NLRA gave mean values of k₃=0.013±0.003 min^-1, k₄=0.011±0.002 min^-1, and DVR=2.29±0.17. Graphical analysis gave a value of DVR=2.28±0.16, and the three ratio values of DVR were: 3-4 h, 2.18±0.15; 4-5 h, 2.34±0.13; and 5-6 h, 2.46±0.19. Graphical analysis was highly correlated with NLRA (R²=0.91, slope=0.90±0.08). The ratio methods correlated well with NLRA (3-4 h, R²=0.71, slope=0.73±0.13; 4-5 h, R²=0.86, slope=0.73±0.09; 5-6 h, R²=0.80, slope=1.00±0.15), and also with graphical analysis (3-4 h, R²=0.65, slope=0.74±0.16; 4-5 h, R²=0.85, slope=0.78±0.09; 5-6 h, R²=0.88, slope=1.11±0.12). The optimum equilibrium time point for obtaining a simple ratio was approximately 4.5-5.5 h. In conclusion, the simple ratio techniques for obtaining a quantitative measure of specific binding correlated well with the reference tissue kinetic models, using both NLRA and graphical analysis. The optimum time for obtaining a ratio appeared to be in the range 4.5-5.5 h. Earlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations. (orig.)

[en] Accurate quantification of neuroreceptors requires full kinetic modeling of the dynamic single-photon emission tomography (SPET) or positron emission tomography (PET) images, with highly invasive arterial blood sampling. This study investigated the application of a reference region kinetic model to the dynamics of [^99mTc]TRODAT-1 in nonhuman primates, obviating the need for blood sampling. A series of dynamic SPET scans were performed on two baboons following the injection of approximately 700 MBq of [^99mTc]TRODAT-1. Rapid arterial blood samples were taken automatically during scanning. Reconstructed SPET images were co-registered with magnetic resonance imaging (MRI) scans of the baboons, and regions of interest (ROIs) placed on the striatum, cerebellum and cerebral hemispheres. The ROI data were combined with metabolite-corrected blood data, and fitted to a three-compartment kinetic model using nonlinear least squares techniques. The same data were also used in a simplified reference region model, in which the input function was derived from the nondisplaceable tissue compartment. In addition, semiquantitative blinded analysis was performed by three raters to determine the point of transient equilibrium in the specific binding curves. All methods generated values for the ratio of the kinetic rate constants k₃/k₄, which gives an estimate of the binding potential, BP. These were compared with the full kinetic model. The mean values of k₃/k₄ for the three different analysis techniques for each baboon were: 1.17±0.21 and 1.12±0.13 (full kinetic model), 0.93±0.13 and 0.90±0.07 (reference region model), and 0.97±0.18 and 0.92±0.08 (equilibrium method). The reference region method gave significantly lower results than the full kinetic model (P = 0.01), but it also produced a much smaller spread and better quality fits to the kinetic data. The reference region model results for k₃/k₄ correlated very strongly with the full kinetic analysis (r² = 0.992, P<0.001), and with the equilibrium model (r² = 0.88, P = 0.002). The subjectivity inherent in the equilibrium method produces inferior results compared with both kinetic analyses. It is suggested that the self-consistency of the reference region model, which requires no arterial blood sampling, provides a more precise and reliable estimate of the binding of [^99mTc]TRODAT-1 to dopamine transporters than full kinetic modeling. The reference region method is also better suited to a routine clinical environment, and would be able to distinguish smaller differences in dopaminergic function between patient groups. (orig.)

[en] Some brain functions decline at a linear rate throughout adulthood. Others remain relatively stable until very late in the life cycle. This study characterized the effects of aging on the regional cerebral distribution of hexamethylpropylene amine oxime (HMPAO) in healthy human volunteers. The sample consisted of 26 men and 18 women with a mean age of 41.6±14.9 years (range: 19-73). Their past medical histories, physical examinations, and laboratory screening tests were normal. Single-photon emission tomography (SPET) scans of the brain were performed with a standardized acquisition and processing protocol on a triple-headed camera equipped with fan beam collimators. A 3-D restorative filter and a correction for uniform attenuation were applied before the images were reinterpolated in planes parallel to the line connecting the frontal and occipital poles. Mean counts per pixel were measured in multiple regions of interest (ROIs) within each hemisphere by custom fitting a set of templates to the images. The mean activity in each ROI was compared with the mean activity per pixel in the whole brain. Regression analyses were used to relate the activity ratios to age with both linear and nonlinear models. The relative concentration of radioactivity decreased significantly with age in most, but not all, gray matter structures. It increased in the white matter regions. The nonlinear model of aging fit the data significantly better than a straight line did. Most of the changes with age occurred during young adulthood. No further changes were detectable after the onset of middle age. The median breakpoint age at which the rate of change became negligible was 36.6 years. Aging significantly affects the relative uptake of HMPAO in healthy humans. It decreases in many gray matter regions and increases in most white matter regions. However, the changes do not appear to be linear. Most seem to occur during young adulthood before people reach their late thirties. (orig./AJ). With 2 figs., 1 tab

[en] IPT [N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane[ is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1-2 h post injection. In the present study [¹²³I[IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40-79 years) and eight age-matched controls were studied. SPET imaging was performed 90-120 min after injection of 160-185 MBq [¹²³I[IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I[IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I[IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I[IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I[IPT binding was significantly correlated with disease duration (r=-0.7, P<0.0001) but not with the age of PD patients (r=-0.10, P=0.61). Specific [¹²³I[IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. (orig./AJ). With 2 figs., 2 tabs