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Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.

ABSTRACT: Quantitative magnetic resonance imaging (MRI) can serially and noninvasively assess the degree of injury in rat pup models of hypoxic ischemic injury (HII). It can also noninvasively monitor stem cell migration following iron oxide prelabeling. Reports have shown that neural stem cells (NSCs) may help mediate neuroprotection or stimulate neuroreparative responses in adult and neonatal models of ischemic injury. We investigated the ability of high-field MRI to monitor and noninvasively quantify the migration, proliferation, and location of iron oxide-labeled NSCs over very long time periods (58 weeks) in real time while contemporaneously correlating this activity with the evolving severity and extent of neural damage.Labeled clonal murine NSCs (mNSCs) were implanted 3 days after unilateral HII in 10-day-old rat pups into the contralateral striatum or ventricle. We developed methods for objectively quantifying key aspects of dynamic NSC behavior (eg, viability; extent, and speed of migration; degree of proliferation; extent of integration into host parenchyma). MRI images were validated with histological and immunohistochemical assessments.mNSCs rapidly migrated (100 ?m/day) to the lesion site. Chains of migrating NSCs were observed in the corpus callosum. In pups subjected to HII, though not in intact control animals, we observed a 273% increase in the MR-derived volume of mNSCs 4 weeks after implantation (correlating with the known proliferative behavior of endogenous and exogenous NSCs) that slowly declined over the 58-week time course, with no adverse consequences. Large numbers of now quiescent mNSCs remained at the site of injury, many retaining their iron oxide label.Our studies demonstrate that MRI can simultaneously monitor evolving neonatal cerebral injury as well as NSC migration and location. Most importantly, it can noninvasively monitor proliferation dynamically for prolonged time periods. To be able to pursue clinical trials in newborns using stem cell therapies it is axiomatic that safety be insured through the long-term real time monitoring of cell fate and activity, particularly with regard to observing unanticipated risks to the developing brain. This study supports the feasibility of reliably using MRI for this purpose.

SUBMITTER: Obenaus A

PROVIDER: S-EPMC3069664 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.

Obenaus Andre A Dilmac Nejmi N Tone Beatriz B Tian Hou Rou HR Hartman Richard R Digicaylioglu Murat M Snyder Evan Y EY Ashwal Stephen S

Annals of neurology 20101122 2

<h4>Objective</h4>Quantitative magnetic resonance imaging (MRI) can serially and noninvasively assess the degree of injury in rat pup models of hypoxic ischemic injury (HII). It can also noninvasively monitor stem cell migration following iron oxide prelabeling. Reports have shown that neural stem cells (NSCs) may help mediate neuroprotection or stimulate neuroreparative responses in adult and neonatal models of ischemic injury. We investigated the ability of high-field MRI to monitor and noninv ...[more]

PMID: 21387373

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Project description:PurposeTo determine the natural history of imaging findings seen on magnetic resonance imaging (MRI) of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT). Although arterial hyperenhancement is a key feature of untreated HCC, our clinical experience suggested that tumors that never progressed could still show hyperenhancement. Therefore, we undertook a systematic study to test the hypothesis that persistent arterial phase hyperenhancement (APHE) after SBRT is an expected finding that does not suggest failure of treatment.Methods and materialsOne hundred forty-six patients undergoing SBRT for HCC between January 1, 2007, and December 31, 2015, were screened retrospectively using an institutional review board-approved prospectively maintained registry. Inclusion criteria were (1) HCC treated with SBRT, (2) multiphasic MRI ≤3 months before SBRT, (3) up to 1 year of follow-up MRI post-SBRT, and (4) cirrhosis. The exclusion criterion was ≤3 months of locoregional therapy to the liver segment containing the SBRT-treated HCC. Pre- and post-SBRT MRI from up to 3 years were analyzed in consensus by independent pairs of subspecialty-trained radiologists to determine the temporal evolution of major features for HCC and imaging findings in off-target parenchyma.ResultsSixty-two patients with 67 HCCs (Organ Procurement and Transplantation Network imaging criteria [OPTN] 5a [n = 26], OPTN 5b [n = 28], OPTN 5x [n = 7]; Liver Imaging Reporting Data System [LI-RAD]-M [n = 4] and LiRADs-4 [n = 2]) were studied. Tumor size either decreased (66% [44 of 67]) or remained unchanged (34% [23 of 67]) within the first 12 months. Post-SBRT APHE was common (58% [39 of 67]). When graded using modified Response Evaluation Criteria in Solid Tumors at 3 to 6 months, 25% (17 of 67) met criteria for complete response and 75% (50 of 67) met criteria for stable disease.ConclusionsSBRT is an effective locoregional treatment option for HCC. Persistent APHE is common and does not necessarily indicate viable neoplasm; thus, standard response assessment such as modified Response Evaluation Criteria should be used with caution, particularly in the early phases after SBRT therapy.

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Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.

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Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.

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