A multivariate approach to registration of dissimilar tomographic images.

We devised a method to allow for retrospective registration of tomographic images with very different information content, the main emphasis being on sets of positron emission tomography images obtained with different tracers. A multivariate cost-function based on information theory was used as an index of "goodness-of-alignment". The cost-function makes no assumptions regarding the form of the relationship between the two image sets, and is hence very general. Image volumes, with known relative spatial orientation, were simulated for tracers with different uptake patterns and the method was validated by assessing its ability to recover these known orientations. The method was able to recover the known transformations with an accuracy of about 1 mm and 1 degrees along and around all axes, even for tracer combinations with radically different uptake patterns and with large initial misalignment. With the suggested method it is feasible to retrospectively align examinations obtained with different tracers and/or modalities.     

Improved efficiency for MRI-SPET registration based on mutual information

Mutual information has been proposed as a criterion for image registration. The criterion is calculated from a two-dimensional grey-scale histogram of the image pair being registered. In this paper we study how sparse sampling can be used to increase speed performance using the registration algorithm of Maes et al. (IEEE Trans Med Imaging 1997; 16: 187-198) with a focus on registration of MRI-SPET brain images. In particular we investigate how sparse sampling and parameters such as the number of bins used for the grey-scale histograms and smoothing of the data prior to registration affect accuracy and robustness of the registration. The method was validated using both simulated and human data. Our results show that sparse sampling introduced local maxima into the mutual information similarity function when the number of bins used for the histograms was large. To speed up registration while retaining robustness, smoothing of the data prior to registration was used and a coarse to fine subsampling protocol, where the number of bins in the histograms were dependent on the subsampling factor, was employed, For the simulated data, the method was able to recover known transformations with an accuracy of about 1 mm. Using the human data, there were no significant differences in the recovered transformation parameters when the suggested subsampling scheme was used compared with when no subsampling was used, but there was a more than tenfold increase in speed. Our results show that, with the appropriate choice of parameters, the method can accurately register MRI-SPET brain images even when very efficient sampling protocols are used.     

Effect on sensitivity and specificity of mammography screening with or without comparison of old mammograms

Purpose:
To evaluate the effect of old mammograms on the specificity and sensitivity of radiologists in mammography screening.
Material and Methods:
One hundred and fifty sets of screening mammograms were examined by 3 experienced screeners twice: once without and once in comparison with older mammograms. The films came from a population-based screening done during the first half of 1994 and comprised all 35 cancers detected during screening in 1994, 12/24 interval cancers, 14/34 cancers detected in the following screening and 89 normal mammograms.
Results:
Without old mammograms, the screeners detected an average of 40.3 cancers (range 37-42), with a specificity of 87% (85-88%). With old mammograms, the screeners detected 37.7 cancers (range 34-42) with a specificity of 96% (94-99%). The change in detection rate was not significant. However, the increase in specificity was significant for each screener (p=0.0002-0.03).
Conclusion:
Mammography screening with old mammograms available for comparison decreased the false-positive recall rate. The effect on sensitivity, however, was unclear.     

Local breast cancer recurrence caused by mammographically guided punctures

Purpose: To evaluate the risk of needle track seeding or tumor cell implantation as the cause of locally recurrent breast cancer after breast conserving surgery.Material and Methods: We reviewed recurrences from a consecutive series of 303 clinically nonpalpable breast cancers treated with breast conserving surgery after pre-operative localization. The median mammographic follow-up was 5.4 years. The suspicion of seeding or implantation was based on the location of the recurrent lesion in comparison with the needle path in two orthogonal mammographic projections. Pre-operative percutaneous biopsies had been done in 71% (214/303) of the cases. Postoperative radiotherapy was administered to 82% (194/238) of the invasive cancers and to 28% (18/65) of the ductal cancers in situ (DCIS).Results: Locally recurrent cancer occurred in 11% (33/303) of the cases. Radiotherapy demonstrated a protective effect from relapse among invasive cancers but not for DCIS. Seeding or implantation was suspected in 3 recurrent invasive cancers which had not been subject to radiotherapy. The histopathological diagnosis of the primary cancer and the recurrent cancer were the same in these cases: adenoid cystic, mucinous and tubuloductal cancer.Conclusion: Seeding or implantation was suspected as the cause of local recurrence in 7% (3/44) of the invasive cancers which did not receive radiotherapy.     

Evaluation by Markov chain models of a non-randomised breast cancer screening programme in women aged under 50 years in Sweden

STUDY OBJECTIVE: To apply Markov chain models that have previously been used on data in randomised trials of breast cancer screening to data from an uncontrolled service screening programme; to compare results with those from a randomised trial. DESIGN: A service screening programme in Uppsala county, Sweden, inviting 25,660 women aged 39-49 to mammographic screening every 20 months, and the Swedish Two-County Trial inviting 19,844 women aged 40-49 to two yearly screening, compared with 15,604 women of the same age in an unscreened control group. Data were analysed using Markov chain models and quasi- likelihood estimation procedures. MAIN RESULTS: The results with respect to parameters of disease progression were very similar between the two studies. Use of estimated progression rates to predict the effect on mortality ranged from a 10% to a 17% reduction in breast cancer mortality in the Two-County Study and predicted a 15% reduction in the Uppsala programme. These compare well with the observed mortality reduction of 13% in the Two-County Trial. CONCLUSIONS: The screening in the Uppsala programme is likely to have a similar effect to that observed in the Two-County Trial. It is feasible to evaluate non-randomised service screening programmes using Markov chain models.     

Accuracy of reported weight and menstrual status in teenage girls with eating disorders

OBJECTIVE: The current study investigated the accuracy of reported current and historical weights and of menstrual status in teenage girls with eating disorders. METHOD: Reported current weight in one interview was compared with measured weight at another occasion. Reported historical weights were compared with documented weights from growth charts of the school health services. Reports of menstrual status from two different interviews were compared. RESULTS: The overall correlation between reported and measured/documented weight was high. Current weight was reported with high accuracy in all diagnostic groups and without tendencies to underreport. Patients with bulimia nervosa, but not those with anorexia nervosa, underreported their historical top weight. The most common reason for large discrepancies between reported and documented historical weights was that the two weights compared referred to different time points. The reports on menstrual status were divergent for 13% of the patients, most notably 4 of 15 patients on oral contraceptives had been categorized as having menstruations in one of the interviews. CONCLUSION: Reported weight history and menstrual status are of high accuracy in teenage girls with eating disorders.     

Endogenous p63 acts as a survival factor for tumour cells of SCCHN origin

The human p63 gene encodes a series of proteins that differ in their N- and/or C-terminal sequences and have widely differing properties in promoting or repressing p53-related functions such as growth arrest and apoptosis. In addition, p63 has important roles in the maintenance and differentiation of epithelial cell populations. Squamous cell carcinomas of the head and neck (SCCHN) express high levels of DeltaNp63 and p63beta isoforms compared to normal tissue from the same patients, suggesting a role for these isoforms in the pathogenesis of this common human malignancy. Here, we explore the function of p63 in SCCHN cells by using small interfering RNA (siRNA) to silence the expression of different isoforms in two SCCHN cell lines, FaDu and SCC-25. Silencing results in statistically significant decreased survival for tumour cells when all p63 isoforms, the N-terminal truncated or the alpha isoforms are inhibited. No effect was observed on cell proliferation or on the expression of epithelial differentiation markers. We also demonstrate that inhibition of endogenous p63 expression sensitises cells to the effects of ionizing radiation and cisplatin, common treatments for SCCHN patients. The data indicate that p63 has oncogenic properties in SCCHN and is predominantly involved in maintaining cell survival, rather than acting as a directly proliferative factor or as an inhibitor of terminal differentiation. Moreover, targeted inhibition of p63 expression in SCCHN could be a useful adjunct for conventional treatments of this disease.     

The influence of a false-positive mammogram on a woman's subsequent behaviour for detecting breast cancer

The aim was to investigate the influence of undergoing further examinations due to a false-positive mammogram on women's re-attendance at the next scheduled screening and their frequency of breast self-examination (BSE). Study participants included 517 women (62% response) recalled due to findings on screening mammograms indicating possible malignancies, and a matched control group of 285 women (68% response) with normal mammograms. Participants completed five and three questionnaires, respectively, during the 2 years following screening participation. While the groups did not differ significantly in screening re-attendance, women recalled due to false-positive mammograms reported significantly higher levels of anxiety related to the next screening than did women with normal mammograms. At the 1-year assessment, women with false-positive mammograms reported a significantly higher frequency of BSE than did women with normal mammograms. The present results indicate that being recalled due to a false-positive mammogram does not seem to negatively affect screening re-attendance, and may have a positive impact on BSE.     

Mapping pathological (99m)Tc-d,l-hexamethylpropylene amine oxime uptake in Alzheimer's disease and frontal lobe dementia with SPECT

Seventeen patients with probable Alzheimer's disease (AD), 7 patients with frontal lobe dementia (FLD) and 19 control subjects (NOR) were examined by (99m)Tc-d,l- hexamethylpropylene amine oxime ((99m)Tc-HMPAO) SPECT. Images were standardised in the same 3D space and averaged within each group. After normalisation, the three sets of images were analysed in all cerebral lobes, hippocampus, thalamus and basal ganglia. In AD, the (99m)Tc-HMPAO uptake values were significantly reduced, as compared to NOR, in the parietal, temporal and insular lobes. In patients with FLD, the uptake was altered in all lobes with the exception of the parietal lobe. The uptake in the nucleus caudatus decreased significantly in both AD and FLD as compared to NOR. The uptake in the anterior cingulate cortex was significantly reduced in FLD. Subtraction images highlighted all significantly decreased areas. In conclusion, standardising SPECT in a common space and subtracting data from a control group improves the visual interpretation of images. In this study, the typical temporo-parietal and fronto-parietal (99m)Tc-HMPAO uptake reductions were found in AD and FLD, respectively. The uptake in the nucleus caudatus was found to decrease significantly in AD and FLD and the one in the anterior cingulate cortex was reduced in FLD.