Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma.

BACKGROUND AND PURPOSE: Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point. MATERIALS AND METHODS: Twenty-three patients with suspected post-chemoradiotherapy glioblastoma progression underwent ferumoxytol-enhanced SWI. Segregation and extravascular localization of ferumoxytol imaging maps were generated as the voxelwise difference of the delayed (24 hours) from the early (immediately after administration) time point SWI maps. Continuous segregation and extravascular localization of ferumoxytol imaging map values were separated into positive and negative components. Image-guided biologic correlation was performed. RESULTS: Negative segregation and extravascular localization of ferumoxytol imaging values correlated with early and delayed time point SWI values, demonstrating that intravascular signal detected in the early time point persists into the delayed time point. Positive segregation and extravascular localization of ferumoxytol imaging values correlated only with delayed time point SWI values, suggesting successful detection of the newly developed extravascular signal. CONCLUSIONS: Segregation and extravascular localization of ferumoxytol MR imaging improves on current techniques by eliminating intrinsic tissue and intravascular ferumoxytol signal and may inform glioblastoma outcomes by serving as a more specific metric of macrophage content compared with uncorrected T1 and SWI techniques.

Management of chronic severe pain: cerebral neuromodulatory and neuroablative approaches.

Two approaches are utilized when targeting the brain to treat pain. The first, a non-destructive approach, uses either electrical stimulation of brain targets thought to modulate the process of pain perception, or pharmacological agents are introduced into ventricular spaces to target pain modulating receptors. Electrical stimulation targets include; the thalamic nuclei, the periventricular and periaqueductal grey (PVG and PAG) matter or the motor cortex. Currently, the pharmacological agent of choice for intracerebroventricular injection is morphine. In general, electrical stimulation is used for nonmalignant type pain, and pharmacological modulation for malignant type pain. The second, a destructive approach, is usually employed with the goal of interrupting the signals that lead to pain perception at various levels. Neuroablation is usually performed on cellular complexes such as "nuclei, or gyri" or on tracts with the aim of disrupting the sensory and limbic pathways involved in the emotional processes associated with pain. Specific cerebral neuroablation targets include; the thalamic medial group of nuclei, the cingulated gyrus, and the trigeminal nucleus and tract. There are fewer reports in the literature detailing the brain, when compared to the spine, as a target to treat pain, and further research is required.

Management of chronic severe pain: spinal neuromodulatory and neuroablative approaches.

The spinal cord is the target of many neurosurgical procedures used to treat pain. Compactness and well-defined tract separation in addition to well understood dermatomal cord organization make the spinal cord an ideal target for pain procedures. Moreover, the presence of opioid and other receptors involved in pain modulation at the level of the dorsal horn increases the suitability of the spinal cord. Neuromodulative approaches of the spinal cord are either electrical or pharmacological. Electrical spinal cord modulation is used on a large scale for various pain syndromes including; failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), neuropathic pain, angina, and ischemic limb pain. Intraspinal delivery of medications e.g. opioids is used to treat nociceptive and neuropathic pains due to malignant and cancer pain etiologies. Neuroablation of the spinal cord pain pathway is mainly used to treat cancer pain. Targets involved include; the spinothalamic tract, the midline dorsal column visceral pain pathway and the trigeminal tract in the upper spinal cord. Spinal neuroablation can also involve cellular elements such as with trigeminal nucleotomy and the dorsal root entry zone (DREZ) operation. The DREZ operation is indicated for phantom type pain and root avulsion injuries. Due to its reversible nature spinal neuromodulation prevails, and spinal neuroablation is performed in a few select cases.