Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia.

Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson's disease, Alzheimer's disease, and schizophrenia. Mapping reactive microglia in-vivo is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure in vivo holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons-a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an in-vivo marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases.

Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite available therapeutic options, the prognosis for patients with GBM remains very poor. We hypothesized that the intra-operative injection of a photopolymerizable hydrogel into the tumor resection cavity could sustain the release of the anti-cancer drug paclitaxel (PTX) encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles and prevent GBM recurrence. The tumor was resected 13 days after implantation and a pre-gel solution composed of polyethylene glycol dimethacrylate (PEG-DMA) polymer, a photoinitiator and PTX-loaded PLGA nanoparticles (PTX PLGA-NPs) was injected into the tumor resection cavity. A solid gel filling the whole cavity was formed immediately by photopolymerization using a 400 nm light. PTX in vitro release study showed a burst release (11%) in the first 8 h and a sustained release of 29% over a week. In vitro, U87 MG cells were sensitive to PTX PLGA-NPs with IC50 level of approximately 0.010 µg/mL. The hydrogel was well-tolerated when implanted in the brain of healthy mice for 2 and 4 months. Administration of PTX PLGA-NPs-loaded hydrogel into the resection cavity of GBM orthotopic model lead to more than 50% long-term survival mice (150 days) compared to the control groups (mean survival time 52 days). This significant delay of recurrence is very promising for the post-resection treatment of GBM.

Immediate post-operative MRI suggestive of the site and timing of glioblastoma recurrence after gross total resection: a retrospective longitudinal preliminary study.

OBJECTIVES: To retrospectively identify morphological and physiological post-operative magnetic resonance imaging (MRI) characteristics predictive of glioblastoma recurrences after gross total resection (gross-TR). METHODS: Resection margins of 24 glioblastoma were analysed immediately post-operatively (MRI ≤ 2 h) and early post-operatively (24 h ≤ MRI ≤ 48 h), and subdivided into areas with and without subtle contrast enhancement previously considered non-specific. On follow-up MRI, tumour regrowth areas were subdivided according to recurrence extent (focally/extended) and delay (≤6 and ≥12 months). Co-registration of pre-operative, immediately post-operative and early post-operative MRI with the first follow-up MRI demonstrating recurrence authorised their morphological (contrast enhancements) and physiological (rCBV) characterisation. RESULTS: Morphologically, on immediately post-operative MRI, micro-nodular and frayed enhancements correlate significantly with early recurrences (≤6 months). After gross-TR the absence of these enhancements is associated with a significant increase in progression-free survival (61 vs 15 weeks respectively) and overall survival (125 vs 51 weeks respectively). Physiologically, areas with a future focal recurrence have a trend toward higher rCBV than other areas. CONCLUSION: Immediately post-operative topography of micro-nodular and frayed enhancements is suggestive of recurrence location and delay. Absence of such enhancements is associated with a fourfold increase in progression-free survival and a 2.5-fold increase in overall survival. KEY POINTS: • Immediately post-operative MRI reveals contrast enhancement after glioblastoma gross total resection. • Immediately post-operative micro-nodular and frayed enhancement correlate with early recurrence. • Absence of micro-nodular/frayed enhancement is associated with 61 weeks' progression-free survival. • Absence of micro-nodular/frayed enhancement is associated with 125 weeks' overall survival.

Intraoperative magnetic resonance imaging at 3-T using a dual independent operating room-magnetic resonance imaging suite: development, feasibility, safety, and preliminary experience.

OBJECTIVE: A twin neurosurgical magnetic resonance imaging (MRI) suite with 3-T intraoperative MRI (iMRI) was developed to be available to neurosurgeons for iMRI and for independent use by radiologists. METHODS: The suite was designed with one area dedicated to neurosurgery and the other to performing MRI under surgical conditions (sterility and anesthesia). The operating table is motorized, enabling transfer of the patient into the MRI system. These two areas can function independently, allowing the MRI area to be used for nonsurgical cases. We report the findings from the first 21 patients to undergo scheduled neurosurgery with iMRI in this suite (average age, 51 +/- 24 yr; intracranial tumor, 18 patients; epilepsy surgery, 3 patients). RESULTS: Twenty-six iMRI examinations were performed, 3 immediately before surgical incision, 9 during surgery (operative field partially closed), and 14 immediately postsurgery (operative field fully closed but patient still anesthetized and draped). Minor technical dysfunctions prolonged 10 iMRI procedures; however, no serious iMRI-related incidents occurred. Twenty-three iMRI examinations took an average of 78 +/- 20 minutes to perform. In three patients, iMRI led to further tumor resection because removable residual tumor was identified. Complete tumor resection was achieved in 15 of the 18 cases. CONCLUSION: The layout of the new complex allows open access to the 3-T iMRI system except when it is in use under surgical conditions. Three patients benefited from the iMRI examination to achieve total resection. No permanent complications were observed. Therefore, the 3-T iMRI is feasible and appears to be a safe tool for intraoperative surgical planning and assessment.