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V Sossi

Publications and source records attributed to V Sossi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3.

The gene-rich telomeric region of 21q harbors several loci relevant to human diseases including autoimmune polyglandular disease type I, nonsyndromic deafness, Knobloch syndrome, holoprosencephaly, and bipolar affective disorder. A contig of genomic clones in this region would facilitate the isolation of these genes. However, distal 21q22.3 has yet been poorly mapped, presumably due to the presence of sequences that are underrepresented in yeast artificial chromosome (YAC) libraries. We generated a framework of YACs and used these clones as starting points for the isolation of a combination of bacterial artificial chromosome clones, P1-derived artificial chromosome clones, and cosmid clones by chromosome walking procedures. These studies resulted in the construction of a high-resolution contig map spanning the 2.5-Mb region from PFKL to the telomere, approximately 2 Mb of which are covered by ready-to-sequence contigs. Within this map we determined the location and relative distance of 21 markers. These include 9 established genetic markers, the order of which is cen-PFKL-D21S154-D21S170-D21S171-D21S1903- D21S1897- D21S112-D21S1446-D21S1575-tel. Moreover, we established the precise map position of 13 genes and 4 ESTs including the recently isolated genes C21ORF2, SMT3H1, RNA editing deaminase 1 (ADARB1), folate transporter (SLC19A1), COL18A1, lanosterol synthase (LSS-PEN), pericentrin (PCNT), and arginine methyltransferase (HRMT1L1). This integrated map provides a useful resource for the mapping and isolation of disease genes and for the construction of a complete transcription map of distal 21q as well as for large-scale sequencing efforts.

Chromosome Mapping↗
PubMed1998

Normalization for 3D PET with a low-scatter planar source and measured geometric factors.

For 3D PET normalization methods, a balance must be struck between statistical accuracy and individual detector or line-of-response (LOR) fidelity. Methods with potentially the best LOR accuracy tend to be statistically poor, while techniques to improve the statistical quality tend to reduce the individual detector fidelity. We have developed and implemented a 3D PET normalization method for our ECAT 953B scanner (Siemens/CTI) that determines the detector normalization factors (NFs) as a product of a four-dimensional matrix of measured geometric factors (GFs) and single detector efficiency factors (epsilon). The effects of various alterations to the algorithm on the accuracy of the normalization have been examined through the impact on reconstructed images. An accurate set of GFs is crucial, as inaccurate NFs can result if LORs with similar but not identical geometric symmetries are grouped together. The general method can be extended to other tomographs, although the dimensionality of a GF matrix may be scanner-specific; the key is to determine the optimal number of dimensions in the GF matrix. The GFs for our scanner are specified by: (i) the two detector rings for each LOR; (ii) the radial distance of the LOR from the tomograph centre; and (iii) the positions within the detector block of the two crystals defining the LOR. Some residual radial non-uniformities are present in all the NF variations we examined. For the NF method presented here, the radial non-uniformities are attributed to the interaction between object-dependent scatter and normalization. Results indicate that this non-uniformity is detectable for scans with as few as 13 million total counts.

Calibration↗
PubMed1998

A phantom study evaluating the quantitative aspect of 3D PET imaging of the brain.

Phantom studies are used to develop a reliable quantitative data processing protocol for 3D PET brain scanning for conditions typically encountered in FDG and neuroreceptor brain imaging. These protocols often span several half-lives of the injected radiotracer thus resulting in a greatly varying statistical content of the acquired data over the study duration. Detector normalization, scatter correction and their interplay over a wide range of statistical content of acquired data were evaluated. Overall sensitivity calibration factors were determined after all other quantification corrections were applied to the data. The result is an optimum data processing protocol that includes an iterative convolution subtraction scatter correction method, a normalization procedure that takes into account the geometric properties of the scanner and a region of interest based calibration procedure, applied in this order. This protocol yields a 3D PET quantification accuracy within approximately 3% of independently measured concentration values for scanning conditions that include variation in the number of acquired counts from one million to several hundred millions and variation in size and shape from a 20 cm diameter phantom to a tapered phantom with minimum cross section of 3.7 x 14.5 cm2. This performance is comparable with that of the 2D acquisition mode.

Algorithms↗
PubMed1998

Quantitative comparison of three- and two-dimensional PET with human brain studies.

UNLABELLED: The aim of this study was to test the quantitation accuracy of three-dimensional PET in brain scanning. METHODS: Three-dimensional data from 11 human subjects were tested using 11C-dihydrotetrabenazine, 11C-Schering 23390 and 18F-FDG as tracers. Two-dimensional scans were performed on the same subjects and the distribution volume, distribution volume ratio and local metabolic rate of glucose (LMRGlu) values obtained from these were used as reference. Three-dimensional data were processed as follows: iterative convolution subtraction scatter correction, detector normalization including radial and axial geometric factors, attenuation correction extracted from a two-dimensional transmission scan, Kinahan-Rogers reconstruction and region-of-interest-based sensitivity calibration. RESULTS: No major systematic differences between the two methods were found. The agreement between the two-dimensional and three-dimensional data was within 5%. Although statistical analysis generally did not show this difference to be significant, reliability analysis indicated that comparing two-dimensional and three-dimensional data might introduce some inaccuracies. CONCLUSION: Three-dimensional PET yields quantitatively valid results for brain scanning.

Adult↗
PubMed1997

Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry.

1. Until recently studies of intestinal aluminium absorption used pharmacological amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts of different chemical compounds of aluminium, in the present study we have employed the long half-life isotope of aluminium, 26Al, and accelerator mass spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate, citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were administered to four groups of rats (n = 9 per group) by gavage. Blood and urine samples were collected for 5 h and the 26Al content (as a percentage of the administered dose) determined by accelerator mass spectrometry. 3. The 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1 +/- 0.1% of administered dose in the four groups respectively. There was a strong positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al excretion in individual animals (P < 0.001). 4. We conclude that the fractional intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads). Absorption of aluminium citrate given alone is significantly greater (0.7%) and is further increased to 5% by the accompanying sodium citrate, consistent with an enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium maltolate absorption approximates that of aluminium hydroxide (0.1%).

Aluminum↗
PubMed1997

Graphical analysis of 6-fluoro-L-dopa trapping: effect of inhibition of catechol-O-methyltransferase.

UNLABELLED: Graphical methods to analyze tracer time-course data allow reliable quantitation of the rate of incorporation of tracer from plasma into a "trapped" kinetic component, even when the details of the kinetic model are unknown. Applications of the method over long time periods often expose the slow reversibility of the trapping process. In the extended graphical method, both trapping rate and a presumed first-order loss rate constant are estimated simultaneously from the time-course data. METHODS: We applied the extended graphical method to 6-fluoro-L-dopa (6-FD), simultaneously estimating the rate of uptake (Ki) and the rate constant for loss from the trapped component (K(loss)) in a single fitting procedure. We applied this approach to study the effects of two catechol-O-methyl-transferase inhibitors on the kinetics of 6-FD in cynomolgus monkeys. RESULTS: Inhibition of peripheral O-methylation with either inhibitor, confirmed by high-performance liquid chromatography analysis of labeled compounds in arterial plasma, had no significant effect on Ki, in agreement with previously reported studies. In contrast, tolcapone, a catechol-O-methyl-transferase inhibitor, having central effects in addition to peripheral effects at the dosage used, decreased K(loss) by 40% from control values (p < 0.002), whereas nitecapone, which has no known central activity, had no significant effect. CONCLUSION: This method provides insight into the neurochemical basis for the kinetic behavior of 6-FD in both health and disease and may be used to define the action of centrally active drugs that influence the metabolism of dopamine.

Animals↗
PubMed1994

The performance of the single-slice rebinning technique for imaging the human striatum as evaluated by phantom studies.

The single-slice rebinning (SSRB) technique has been implemented on a ring-based tomograph with removable septa and its performance evaluated with phantom studies. The studies involved the determination of the plane efficiency profile and the mapping of the point spread function. The image quality obtained using the SSRB technique has been compared to that obtained using the standard 3D reconstruction method in terms of the following figures of merit: recovery as a function of source axial position and slice averaging, contrast recovery and contrast to background noise ratio as a function of source axial position. The effect of the region of interest (ROI) size on such a comparison has been evaluated. Finally the effects of different contrast conditions and ROI position on a striatal phantom image have been thoroughly explored.

Algorithms↗
PubMed1994

Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry.

A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study.

Aluminum↗
PubMed1993

Parametric imaging of the rate constant Ki using [18Fluoro]-L-dopa positron emission tomography in progressive supranuclear palsy.

Positron emission tomography (PET) studies using [18F]-L-dopa were carried out in 9 patients with supranuclear palsy and 13 controls. For quantification of PET data a rate constant Ki was calculated for the radiotracer using a graphical method. Corrections for nonspecific activity were performed in both arterial plasma and brain tissue. The purpose of this study was to test the hypothesis that parametric images of the rate constant K mapping can be obtained on a pixel-by-pixel basis using an appropriate mathematical algorithm. Ki values from these parametric images and the graphical approach were compared. Both correlated closely, with y = 0.013 + 0.947*x, r = 0.992 and y = -0.052 + 1.018*x, r = 0.965 in patients and controls, respectively. Contrast measurements were also performed and showed a striking increase in contrast on parametric images. K mapping offers several advantages over the graphical approach, since parametric images are time-independent, i.e. one image represents the quantitative result of the study. In addition, parametric images of the rate constant are normalized to arterial plasma radioactivity and corrected for tissue metabolites. Thus, parametric images of Ki in different individuals can be compared directly without further processing in order to assess the nigrostriatal integrity.

Aged↗
PubMed1993

Recovery of the human striatal signal in a slice oriented positron emission tomograph.

The human striatum is small enough for partial volume effects to be important when imaged in positron tomographs with slice widths 10 mm or greater. The combination of interslice distance and slice width in such tomographs results in an axial undersampling of the striatal activity which introduces the additional problem of variation of axial recovery as a function of position of the striatum along the tomograph axis. Using striatal phantoms, we have developed a method that corrects the recovered striatal signal to a maximum value equivalent to that measured when the object is centered with respect to a slice. This makes the recovery independent of the axial position of the striatum. The method also provides an estimate of the total striatal activity by integrating the axial image intensity distribution along the tomograph axis. The method is able to detect and correct for relative axial tilt of the left and right striatum. We applied it to 26 human [18F]-6-L-fluorodopa scans and obtained an average uptake rate constant k value of 0.25 +/- 0.05 ml/min/striatum and a left to right k value percentage asymmetry of 0.1% +/- 6.3%.

Adult↗
PubMed1992

[L-18F-dopa-PET in Parkinson-plus syndromes for the detection of a disordered presynaptic dopaminergic function].

PET examinations using L-18F-DOPA were performed on 14 patients with Parkinsonism-plus syndromes (PPLUS). A rate constant Ki was calculated by a graphical method using an arterial input function. Sequential PET images were obtained and no specific activity was measured both in cortical and cerebellar background regions. These results were compared with those in 20 normal controls and tested for intra- and interobserver variability. All patients with PPLUS showed reduced Ki values with a mean of 0.154 (ml/striatum/min), whereas controls exhibited Ki values with a mean of 0.690 (ml/striatum/min) using cortical background regions. The correlation coefficient was calculated to be r = 0.973 for the intraobserver variability and r = 0.879 for the interobserver variability in controls, and r = 0.989 or = 0.973 in PPLUS, resp. There was no significant difference in the Ki values for cortical and cerebellar background regions (p = 0.1). PET examinations using L-18F-DOPA can reliably assess the extent of nigrostriatal degeneration in vivo. Since this radiotracer binds irreversibly within the striatum PET examinations allow the quantification of a disturbed dopaminergic function which is observer-independent.

Aged↗