Cellular magnetic resonance imaging (MRI) is an evolving field of imaging with strong translational and research potential. The ability to detect, track, and quantify cells in vivo and over time allows for studying cellular events related to disease processes and may be used as a biomarker for decisions about treatments and for monitoring responses to treatments. In this review, we discuss methods for labeling cells, various applications for cellular MRI, the existing limitations, strategies to address these shortcomings, and clinical cellular MRI.

OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB), which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2 + breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI) to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2) were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105) across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05); interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001). Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05) in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2 + breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

BackgroundLung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. As there is no consensus regarding the optimal radiotherapy treatment regimen for these tumors, we performed a modeling study to evaluate the trade-offs between predicted toxicity and local control for commonly used high-precision dose-fractionation regimens.MethodsTen patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for 3 different hypofractionated schemes: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each regimen, one plan was created that prioritized planning target volume (PTV) coverage, potentially at the expense of organ at risk (OAR) tolerance, and a second that compromised PTV coverage to respect OAR dose constraints. Published radiobiological models were employed to evaluate competing treatment plans based on estimates for local control and the likelihood for toxicity to OAR.ResultsThe risk of esophageal or pulmonary toxicity was low (< 5%) in all scenarios. When PTV coverage was prioritized, tumor control probabilities were 92.9% for 50 Gy in 5 fractions, 92.4% for 60 Gy in 8 fractions, and 52.0% for 60 Gy in 15 fractions; however the estimated risk of grade ≥ 4 toxicity to the proximal bronchial tree was 68%, 44% and 2% respectively. When dose to OAR was prioritized, the risk of major pulmonary toxicity was reduced to < 1% in all schemes, but this compromise reduced tumor control probability to 60.3% for 50 Gy in 5 fractions, 65.7% for 60 Gy in 8 fractions and 47.8% for 60 Gy in 15 fractions.ConclusionsThe tradeoff between local control and central airway toxicity are considerable in the use of 3 commonly used hypofractionated radiotherapy regimens for ultra-central lung cancer. The results of this planning study predict that the best balance may be achieved with 60 Gy in 8 fractions compromising PTV coverage as required to maintain acceptable doses to OAR. A prospective phase I trial (SUNSET) is planned to further evaluate this challenging clinical scenario.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1001-6) contains supplementary material, which is available to authorized users.

MnAMP, a cell-trappable pro-contrast agent gets enzymatically activated and accumulated intracellularly to provide a strong MRI signal for cell labeling.