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The developing brain is particularly vulnerable to fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders through to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, an anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. Using a preclinical FGR piglet model, ibuprofen was administered for three days from birth. FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident where plasma protein leakage was present, suggestive of structural deficits to the NVU. A significant increase in peripheral infiltrates were also evident in the parenchyma of FGR piglet brains. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen also attenuated plasma protein leakage, regained astrocytic end-feet interaction around vessels, and decreased T-cell infiltration into the FGR brain. These findings suggest postnatal administration of ibuprofen modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.

The developing brain is particularly vulnerable to foetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, an anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. Using a preclinical FGR piglet model, ibuprofen was orally administered for 3 days from birth. FGR brains demonstrated a proinflammatory state, with changes to glial morphology (astrocytes and microglia), and blood-brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident where plasma protein leakage was present, suggestive of structural deficits to the NVU. T-cell infiltration was also evident in the parenchyma of FGR piglet brains. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing the number of activated microglia and enhancing astrocyte interaction with blood vessels. Ibuprofen also attenuated plasma protein leakage, regained astrocytic end-feet interaction around vessels, and decreased T-cell infiltration into the FGR brain. These findings suggest postnatal administration of ibuprofen modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. Modulation of the NVU improves the FGR brain microenvironment and may be key to neuroprotection.

Pathophysiologic mechanisms underpinning ongoing pain in whiplash-associated disorder (WAD) are not well understood, however, alterations in brain morphology and function have been observed in this population and in other chronic pain conditions. This study investigated metabolite profiles of brain regions in people with chronic WAD compared with controls.Thirty-eight individuals with chronic WAD (mean [SD] age, 39.5 [11.3] years, 23 female individuals) and 16 pain-free controls (38.9 [12.7] years, 11 female individuals) underwent multivoxel brain magnetic resonance spectroscopy. At the anterior cingulate cortex (ACC), primary motor cortex (1MC), and somatosensory cortex (SSC), ratios of metabolite concentrations were calculated for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (Ins), and glutamate/glutamine (Glx). Chronic WAD group participants completed clinical questionnaires and cold and pressure pain threshold assessment. Data were analyzed with hypothesis testing and Spearman correlations (P≥0.05), with Benjamini-Hochberg corrections (5% false discovery rate).No group differences were observed for NAA:Cr, NAA:Cho, Cr:Cho, Glx:NAA, Glx:Cr, Glx:Cho, Ins:NAA, Ins:Cr, Ins:Cho or Ins:Glx for left or right ACC, 1MC, or SSC following correction for multiple comparisons. No significant correlations were observed between metabolite ratios and any clinical variable.These results suggest that ongoing pain and disability in this population may not be underpinned by metabolite aberrations in the brain regions examined. Further research is required to progress our understanding of cortical contributions to neurophysiologic mechanisms in chronic WAD.

Descriptions of the radiological appearance of the craniovertebral ligaments often lack detail. This study aimed to provide an accurate description of the morphology and radiological appearance of the alar and cruciform ligaments with confirmation of findings by fine dissection.Six embalmed human cadaveric specimens were reduced to an osseoligamentous arrangement spanning the C2/3 disc to the occiput. Specimens were imaged on a 4.6T Bruker magnetic resonance (MR) system using a 3D RARE multiple SE sequence with acquisition time 18 h 24 min. Acquired images were viewed in three planes, and detailed descriptions and morphometric measurement of the ligaments were obtained. Specimens were then examined and described using fine dissection. Direct comparison of the descriptions of each method was undertaken.From imaging, detailed features of all alar ligaments could be identified in all specimens. Consistency in shape, orientation, and attachments is described. Attachment to the medial aspect of the atlantooccipital joints was evident in all specimens. Five of six alar ligament pairs contained fibers that traversed the dens without attachment. Ascending cruciform ligaments could be clearly identified in four of six specimens. No descending cruciform ligaments could be clearly delineated. Detailed features of the transverse ligaments could be identified and described in all planes. Dissection findings were mostly consistent with descriptions obtained from MR images.4.6T MR images provide accurate detail of the structure, dimensions, and attachments of the craniovertebral ligaments. The morphology of the craniovertebral ligaments assessed radiologically was consistent with findings on gross dissection.

The main aim of this study was to employ high-resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4-T small-animal MR system was employed for nondestructive imaging of post-mortem, fixed spinal cord specimens at the subacute (7 days) and more chronic (28-35 days) stages post-injury. Routine histological techniques were used for subsequent investigation of the observed neuropathology at the microscopic level. The central core of the lesion appeared as a dark hypo-intense area on MR images at all time points investigated. Small focal hypo-intense spots were also observed spreading through the dorsal funiculi proximal and distal to the site of impact, an area that is known to undergo gliosis and Wallerian degeneration in response to injury. Histological examination revealed these hypo-intense spots to be high in iron content as determined by Prussian blue staining. Quantitative image analysis confirmed the increased presence of iron deposits at all post-injury time points investigated (p0.05). Distant iron deposits were also detectable through live imaging without the use of contrast-enhancing agents, enabling the longitudinal investigation of this pathology in individual animals. Further immunohistochemical evaluation showed that intracellular iron deposits localised to macrophages/microglia, astrocytes and oligodendrocytes in the subacute phase of SCI, but predominantly to glial fibrillary acidic protein-positive, CC-1-positive astrocytes at later stages of recovery. Progressive, widespread intracellular iron accumulation is thus a normal feature of SCI in mice, and high-resolution MRI can be effectively used to detect and monitor these neuropathological changes with time.

Super-resolution reconstruction is a process by which a set of different low resolution images of the same object are used to create an enhanced, higher resolution image of that object. Recently there has been debate amongst researchers whether it is possible to obtain in-plane image enhancement using a set of low resolution magnetic resonance images, acquired by making small, independent changes to the demodulation frequency. We show that shifted low-resolution images contain different information that can be used to obtain denser sampling, leading to image enhancement. We conclude this from specific phantom experiments, applying signal processing sampling theory and taking into consideration the relative sampling of the point spread function with respect to the location of signal sources. Furthermore, the maximum achievable resolution for Fourier encoded MRI data at a boundary or object feature is governed by the effective width of the point spread function or the Fourier pixel size determined by the extent of k-space; this is verified experimentally.

To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes.We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment.There was a significant improvement in glycemic control (glycosylated hemoglobin -0.7 +/- 0.7%, por = 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 +/- 14.5 micro mol glucose/min/kg free fat mass, p0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (por = 0.05) with RSG (2.1 +/- 2.0 kg and 1.4 +/- 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 +/- 28.7 cm(2), p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (-6.7 +/- 9.7%, concentration relative to water).Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.