We compared overexpression of the magnetotactic bacterial gene MagA with the modified mammalian ferritin genes HF+LF, in which both heavy and light subunits lack iron response elements. Whereas both expression systems have been proposed for use in non-invasive, magnetic resonance (MR) reporter gene expression, limited information is available regarding their relative potential for providing gene-based contrast. Measurements of MR relaxation rates in these expression systems are important for optimizing cell detection and specificity, for developing quantification methods, and for refinement of gene-based iron contrast using magnetosome associated genes. We measured the total transverse relaxation rate (R2*), its irreversible and reversible components (R2 and R2′, respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells. Clonal lines overexpressing MagA and HF+LF were cultured in the presence and absence of iron supplementation, and mounted in a spherical phantom for relaxation mapping at 3 Tesla. In addition to MR measures, cellular changes in iron and zinc were evaluated by inductively-coupled plasma mass spectrometry, in ATP by luciferase bioluminescence and in transferrin receptor by Western blot. Only transverse relaxation rates were significantly higher in iron-supplemented, MagA- and HF+LF-expressing cells compared to non-supplemented cells and the parental control. R2* provided the greatest absolute difference and R2′ showed the greatest relative difference, consistent with the notion that R2′ may be a more specific indicator of iron-based contrast than R2, as observed in brain tissue. Iron supplementation of MagA- and HF+LF-expressing cells increased the iron/zinc ratio approximately 20-fold, while transferrin receptor expression decreased approx. 10-fold. Level of ATP was similar across all cell types and culture conditions. These results highlight the potential of magnetotactic bacterial gene expression for improving MR contrast.

Optimization of magnetization-prepared rapid gradient-echo (MP-RAGE) sequence variations for maximum white matter (WM) versus gray matter (GM) contrast in neonates at 3T was investigated. Numerical simulations were applied to optimize and compare three contrast preparation modules and to assess the effect of phase encoding (PE) order on contrast between WM and thin cortical GM layers. Simulations predict that a new sequence, which combines both T₁- and T₂-weighting into the contrast preparation and utilizes an interleaved elliptical-spiral PE order, should provide the strongest contrast between neonatal WM and cortical GM. This sequence was compared to a conventional MP-RAGE acquisition (i.e., T₁-weighted preparation, centric PE order) for in vivo imaging of seven preterm newborn infants. Regional measurements of the contrast-to-noise ratio (CNR) between WM and GM demonstrated an increase of 50–70% (depending on GM region) using the new sequence, in good agreement with theoretical predictions. This improved contrast resulted in superior WM versus GM discrimination in intensity-based brain tissue segmentations. Magn Reson Med 59:1190–1196, 2008.

To determine the effect of dose fractionation and time delay post-neoadjuvant stereotactic ablative radiotherapy (SABR) on dynamic contrast-enhanced (DCE)-MRI parameters in early stage breast cancer patients. DCE-MRI was acquired in 17 patients pre- and post-SABR. Five patients were imaged 6-7 days post-21 Gy/1fraction (group 1), six 16-19 days post-21 Gy/1fraction (group 2), and six 16-18 days post-30 Gy/3 fractions every other day (group 3). DCE-MRI scans were performed using half the clinical dose of contrast agent. Changes in the surrounding tissue were quantified using a signal-enhancement threshold metric that characterizes changes in signal-enhancement volume (SEV). Tumour response was quantified using Ktrans and ve (Tofts model) pre- and post-SABR. Significance was assessed using a Wilcoxin signed-rank test. All group 1 and 4/6 group 2 patients' SEV increased post-SABR. All group 3 patients' SEV decreased. The mean Ktrans increased for group 1 by 76% (p = 0.043) while group 2 and 3 decreased 15% (p = 0.028) and 34% (p = 0.028), respectively. For ve, there was no significant change in Group 1 (p = 0.35). Groups 2 showed an increase of 24% (p = 0.043), and Group 3 trended toward an increase (23%, p = 0.08). Kinetic parameters measured 2.5 weeks post-SABR in both single fraction and three fraction groups were indicative of response but only the single fraction protocol led to enhancement in the surrounding tissue. Our results also suggest that DCE-MRI one-week post-SABR may be too early for response assessment, at least for single fraction SABR, whereas 2.5 weeks appears sufficiently long to minimize confounding acute effects.