Automated core-penumbra quantification in neonatal ischemic brain injury

Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 08/2012; 32(12). DOI: 10.1038/jcbfm.2012.121
Source: PubMed


Neonatal hypoxic-ischemic brain injury (HII) and arterial ischemic stroke (AIS) result in irreversibly injured (core) and salvageable (penumbral) tissue regions. Identification and reliable quantification of salvageable tissue is pivotal to any effective and safe intervention. Magnetic resonance imaging (MRI) is the current standard to distinguish core from penumbra using diffusion-perfusion mismatch (DPM). However, subtle MR signal variations between core-penumbral regions make their visual delineation difficult. We hypothesized that computational analysis of MRI data provides a more accurate assessment of core and penumbral tissue evolution in HII/AIS. We used two neonatal rat-pup models of HII/AIS (unilateral and global hypoxic-ischemia) and clinical data sets from neonates with AIS to test our noninvasive, automated computational approach, Hierarchical Region Splitting (HRS), to detect and quantify ischemic core-penumbra using only a single MRI modality (T2- or diffusion-weighted imaging, T2WI/DWI). We also validated our approach by comparing core-penumbral images (from HRS) to DPM with immunohistochemical validation of HII tissues. Our translational and clinical data results showed that HRS could accurately and reliably distinguish the ischemic core from penumbra and their spatiotemporal evolution, which may aid in the vetting and execution of effective therapeutic interventions as well as patient selection.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 August 2012; doi:10.1038/jcbfm.2012.121.

35 Reads
  • Source
    • "Differentiating core from penumbra by using imaging characteristics of tissue densities as a marker of injury, as in our study, may be equally or more sensitive and specific, as well as it is easier to quantify than currently used methods such as diffusion perfusion mismatch (Ghosh et al., 2012). One of our recent publications has demonstrated how methods such as HRS could potentially be used to examine more subtle thresholds of tissue injury than just examining core versus penumbra (Supplementary Figure 3 in Ghosh et al., 2012). This may be helpful in better quantifying more granular levels of tissue injury and is potentially relevant for neonatal HII, which is considered different than adult HII as there is greater evolving apoptotic/mitochondrial injury in newborns . "
    [Show abstract] [Hide abstract]
    ABSTRACT: While hypothermia (HT) is the standard-of-care for neonates with hypoxic ischemic injury (HII), the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18) or normothermia (NT, 35℃; n = 15). Outcomes included magnetic resonance imaging (MRI), neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII). Lesion volumes (24 hr) were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19). Lesion volumes rebounded at 72 hr (48 hr post-HT) with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β) at all time points (p < .05); monocyte chemoattractant protein-1 (MCP-1) trended toward being decreased in HT pups (p = .09). The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1) was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr), potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury. © The Author(s) 2014.
    ASN Neuro 10/2014; 6(6). DOI:10.1177/1759091414558418 · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), although little is known about white matter changes over time. Methods: Infants with PAIS were serially scanned in the neonatal period (n = 15), at 3 mo (n = 16), and at 24 mo (n = 8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation, and posterior thalamic radiation) were obtained and compared with FA values of healthy controls and neurodevelopmental outcome. Results: In the neonatal period, no differences in FA values were found. At 3 mo, the six infants who ultimately developed motor deficits showed lower FA values in all affected regions. Four infants developed a visual field defect and showed lower FA values in the affected optic radiation at 3 mo (0.22 vs. 0.29; P = 0.03). Finally, a correlation between FA values of the corpus callosum at 3 mo and the Griffiths developmental quotients was found (r = 0.66; P = 0.03). At 24 mo, a similar pattern was observed. Conclusion: Neonatal FA measurements may underestimate the extent of injury following PAIS. FA measurements at 3 mo could be considered a more reliable predictor of neurodevelopmental outcome and correlate with DTI findings at 24 mo.
    Pediatric Research 03/2013; 73(6). DOI:10.1038/pr.2013.45 · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Gender is increasingly recognized as an important influence on brain development, disease susceptibility, and response to pharmacologic/rehabilitative treatments. In regenerative medicine, it remains entirely unknown whether there is an interaction between transplanted stem cells and host gender that might bias efficacy and safety in some patients but not others. Methods: We examined the role of recipient gender in a neonatal rat hypoxic-ischemic injury (HII) model, treated with female human neuronal stem cells (hNSCs), labeled with superparamagnetic iron oxide particles implanted into the contralateral cerebral ventricle. We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability). Results: Recipient gender after implantation did not influence the volume or location of ischemic injury (1, 30, or 90 d) or behavior (90 d). Superparamagnetic iron oxide labeling did not influence HII evolution. Implantation had its greatest benefit on mild/moderate injuries, which remained stable rather than increasing as in severe HII as is the natural history for such lesions. Conclusion: Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human newborns with mild-to-moderate HII.
    Pediatric Research 01/2014; 17(5). DOI:10.1038/pr.2014.7 · 2.31 Impact Factor
Show more