MR coronary artery imaging with 3D motion adapted gating (MAG) in comparison to a standard prospective navigator technique.

Magnetic resonance coronary angiography (MRCA) has been proven to be feasible for imaging of the proximal and medial portions of the three main coronary arteries. Free breathing techniques allow for high resolution imaging but prolong scan time. This could potentially be shortened by improving the efficiency, robustness and accuracy of the navigator gating algorithm. Aim of this study was to determine the feasibility, efficiency, and image quality of a new motion compensation algorithm (3D-MAG) for coronary artery imaging with navigator techniques. In 21 patients the coronaries were imaged in plane with a 3D k-space segmented gradient echo sequence. A T2 preparation prepulse was used for suppression of myocardial signal, during free breathing and a navigator technique with using real time slice following and a gating window of 5 mm was applied to suppress breathing motion artefacts. Imaging was performed with standard gating and compared to 3D-MAG. Image quality was visually compared, contrast-to-noise and signal-to-noise ratio were calculated, the length of visualized coronary arteries was measured and scan duration and scan efficiency were calculated. Standard navigator imaging was feasible in 19 of 21 (90.5%) patients 3D-MAG in 21/21 (100%). Scan efficiency and duration was significantly improved with 3D-MAG (p < .05) without change in image quality. 3D-MAG is superior to conventional navigator correction algorithms. It improves feasibility and scan efficiency without reduction of image quality. This approach should be routinely used for MR coronary artery imaging with navigator techniques.

Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer.

Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung.

Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes 5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA overrepresentations of chromosome 1q and DNA losses on chromosomes 3q, 9q, 10p, and 19, whereas squamous cell carcinomas were characterized by increased overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the first time, we used a histogram representation and statistical analysis to evaluate the differences between both tumor groups. In particular, the overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were significantly associated with adenoid differentiation, whereas the DNA loss of chromosomal band 2q36-37 and the overrepresentations at 3q21-22 and 3q24-qter were statistically significant markers for the squamous cell type. The study strengthens the notion that different tumor subgroups of the respiratory tract are characterized by distinct patterns of chromosomal alterations.

Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations.

Small-cell lung cancer (SCLC) represents a group of highly malignant tumors giving rise to early and widespread metastases. We used comparative genomic hybridization in autoptic tumor specimens from 10 patients to discover genetic alterations that are associated with tumor progression and potentially with the metastatic phenotype. Ten primary SCLC and 16 corresponding metastases were investigated with a maximum of 4 tumors per case. Prevalent changes observed in more than 60% of the primary tumors and their metastases included deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p, and DNA over-representations on chromosomes 3q and 5p. The number of common alterations in the primary tumors and the related metastases outnumbered the differences, indicating a clonal relationship. Within the lesions of the same patient, differences were found between the primary tumor and the metastases as well as between metastases of distinct organ sites. However, no specific alteration was significantly associated with the metastatic phenotype. We suggest that the high malignancy of SCLC is defined by the above-mentioned pattern of aberrations.

Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p.

The genetic mechanisms that define the malignant behaviour of small-cell lung cancer (SCLC) are poorly understood. We performed comparative genomic hybridization (CGH) on 22 autoptic SCLCs to screen the tumour genome for genomic imbalances. DNA loss of chromosome 3p was a basic alteration that occurred in all tumours. Additionally, deletions were observed on chromosome 10q in 94% of tumours and on chromosomes 4q, 5q, 13q and 17p in 86% of tumours. DNA loss was confirmed by loss of heterozygosity (LOH) analysis for chromosomes 3p, 5q and 10q. Simultaneous mutations of these six most abundant genetic changes were found in 12 cases. One single tumour carried at least five deletions. DNA under-representations were observed less frequently on chromosome 15q (55%) and chromosome 16q (45%). The prevalent imbalances were clearly indicated by the superposition of the 22 tumours to a CGH superkaryogram. In our view, the high incidence of chromosomal loss is an indication that SCLC is defined by a pattern of deletions and that the inactivation of multiple growth-inhibitory pathways contributes in particular to the aggressive phenotype of that type of tumour.