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. 2013 Dec 26;8(12):e83045.
doi: 10.1371/journal.pone.0083045. eCollection 2013.

Imaging of an inflammatory injury in the newborn rat brain with photoacoustic tomography

Edgar Guevara  1 , Romain Berti  1 , Irène Londono  2 , Ningshi Xie  2 , Pierre Bellec  3 , Frédéric Lesage  1 , G A Lodygensky  4
Affiliations

Imaging of an inflammatory injury in the newborn rat brain with photoacoustic tomography

Edgar Guevara et al. PLoS One. .

Abstract

Background: The precise assessment of cerebral saturation changes during an inflammatory injury in the developing brain, such as seen in periventricular leukomalacia, is not well defined. This study investigated the impact of inflammation on locoregional cerebral oxygen saturation in a newborn rodent model using photoacoustic imaging.

Methods: 1 mg/kg of lipopolysaccharide(LPS) diluted in saline or saline alone was injected under ultrasound guidance directly in the corpus callosum of P3 rat pups. Coronal photoacoustic images were carried out 24 h after LPS exposure. Locoregional oxygen saturation (SO2) and resting state connectivity were assessed in the cortex and the corpus callosum. Microvasculature was then evaluated on cryosection slices by lectin histochemistry.

Results: Significant reduction of SO2 was found in the corpus callosum; reduced SO2 was also found in the cortex ipsilateral to the injection site. Seed-based functional connectivity analysis showed that bilateral connectivity was not affected by LPS exposure. Changes in locoregional oxygen saturation were accompanied by a significant reduction in the average length of microvessels in the left cortex but no differences were observed in the corpus callosum.

Conclusion: Inflammation in the developing brain induces marked reduction of locoregional oxygen saturation, predominantly in the white matter not explained by microvascular degeneration. The ability to examine regional saturation offers a new way to monitor injury and understand physiological disturbance non-invasively.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Coronal B-scan ultrasound images at the level of the LPS injection.
(A) Arrow marks injection site. (B) Seeds placement, overlaid a coronal B-scan, averaged over 11 individual B-scans. Abbreviations: M, motor cortex; S1, primary somatosensory cortex; S1BF, barrel field primary somatosensory cortex; LV, Lateral ventricle; CPu, Caudate putamen. Black dotted line indicates Left Cortex ROI used for locoregional SO2 measurement. White dotted rectangle indicates ROI used for local SO2 measurement in corpus callosum. Scale bar: 1 mm.
Figure 2
Figure 2. Locoregional cortical saturation (SO2%) following LPS exposure.
(A) Group averaged SO2 weighted PAT image for sham controls (NaCl), (B) Group averaged SO2 weighted PAT image for LPS group, (C) SO2 Comparison performed between LPS group (N = 11), and NaCl (sham) group (N = 8). SO2 showed significant decrease in the LPS group compared to NaCl group in left cortex (L) and corpus callosum (cc). The hemisphere contralateral (R) to injection showed no difference. (D) HbT comparison between LPS and NaCl groups, no significant differences were found in any of the explored ROIs. Scale bar: 1 mm; *P<0.05, ***P<0.001.
Figure 3
Figure 3. TRITC-conjugated lectin staining of brain sections 24h after LPS or saline injection with the associated microvascular skeleton extracted with Angio Tool.
(A) left cortex; sham, (B) left cortex; LPS, (C) right cortex; sham, (D) right cortex; LPS, (E) corpus callosum; sham, (F) corpus callosum; LPS. The average microvessel length in the left cortex of brains injected with LPS (B) is reduced with vessels appearing fragmented compared to the brain injected with saline (A). Bar graphs of total microvessel length (G) and average microvessel length (H) in rat brain sections over the cortex and corpus callosum using the skeleton technique with AngioTool. Note the significant decrease in average microvessel length on the left cortex in brains injected with LPS (* p = 0.0093). Scale bar  = 100 μm.
Figure 4
Figure 4. Regional bilateral functional correlation.
Comparison performed between LPS group (N = 11), and NaCl (sham) group (N = 8); analysis done for every seed time-trace and its contralateral part. Contrasts shown: (A) SO2, (B) HbT (C) HbO2 and (D) HbR. Abbreviations: (M, motor cortex; S1, primary somatosensory cortex; S1BF, barrel field primary somatosensory cortex).
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