Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

Macroprolactinemia: predictability on clinical basis and detection by PEG precipitation with two different immunometric methods.

Prolactin (PRL) in human serum is present in three species: monomeric PRL (23 kDA), big PRL (50-60 kDa) and big, big PRL (bb-PRL or macroprolactinemia) of 150-170 kDa. Macroprolactin seems to be mainly composed of a molecule of monomeric PRL and an immunoglobulin G anti PRL. Its biological activity is considered low or absent, but it is measured, at various degrees, by the immunoassay method, thus causing diagnostic problems. Polyethylene Glycol (PEG) has been employed to precipitate macroprolactin, allowing its detection. This method is not applicable to all immunoassays for technical reasons. Our aim was to evaluate: 1) the predictability of macroprolactin on a clinical basis; 2) the possibility of applying PEG precipitation to Abbott AxSYM analyzer beside Roche Elecsys (already approved). We classified 34 hyperprolactinemic women, on a clinical and imaging basis, in four groups: A: functional hyperprolactinemia; B: pituitary lesions hyperprolactinemia; C: probably macroprolactinemia; D: unclassifiable hyperprolactinemia and a "control" group E of 19 healthy women. PRL was assayed, both with Elecsys and AxSYM, before and after PEG serum treatment. Eleven out of twelve group C, and 5/7 group D patients showed macroprolactinemia, against 1/7 in A and 1/8 in B. PEG was suitable for AxSYM only after the same treatment of the calibration standards, thus performing outcomes overlapping Elecsys. For clinical purposes, in the presence of macroprolactinemia, besides the recovery ratio, molar or ponderal monomeric PRL assay should be calculated.

Identification of IgG-immunocomplex macroprolactin with an immunometric "sandwich" system: technical and clinical considerations.

MacroPRL can be due either to anti-PRL autoantibodies IgG (IgG-macroPRL) or other PRL containing molecules without IgG-PRL immuncomplexes (nIgG-macroPRL), the composition of which is not fully clarified. The aims of this study were: a) testing a new immunometric assay, capable of recognising IgG-macroPRL, b) looking for any biological and/or clinical discrepancy between nlgG-macroPRL and IgG-macroPRL. Clinical, biological and neuroradiological data were recorded from 28 hyperprolactinemic women classified as macroprolactinemic on the basis of PRL recoveries after polyethylene glycol (PEG) precipitation <50% on a Roche Elecsys analyser. Fourteen sera with recoveries >70% were employed as controls for the IgG-macroPRL assay. An immunometric "sandwich" assay for IgG-macroPRL was performed employing an anti-PRL antibody to capture PRL and a second one binding and tracing the immunoglobulin G (IgG) component. For this purpose, 2 kits were simultaneously employed, the first for PRL assay and the second for Anti-Toxoplasma IgG assay. The procedure was applied to both DiaSorin LIAISON and Abbott AxSYM systems. IgG-macroPRL immunometric detection was obtained with DiaSorin LIAISON. Twenty out of 28 (72%) sera gave luminescent signal higher than the maximum control serum and were considered as IgG-macroPRL carriers. Our results confirm the high IgG-macroPRL prevalence in macroprolactinemia. No significant clinical differences appear between IgG and nIgG-macroPRL. Conversely, significantly higher PRL values (p =0,039) and lower recoveries (p = 0.001) were found in IgG-macroPRL. Further studies with reference methods, such as gel chromatography and human IgG (h-IgG) affinity columns, are needed to fully validate this IgG-macroPRL immunometric assay.