Péter Várallyay

Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours

Ferumoxtran‐10 (Combidex®), a dextran‐coated iron oxide nanoparticle, provides enhancement of intracranial tumours by magnetic resonance (MR) for more than 24 h and can be imaged histologically by iron staining. Our goal was to compare ferumoxtran imaging and histochemistry vs. gadolinium enhancement in malignant brain tumours on preoperative and postoperative MR. Methods: Seven patients with primary and metastatic malignant tumours underwent MR imaging with gadolinium and ferumoxtran both pre‐ and postoperatively. Normalized signal intensities on the ferumoxtran‐enhanced scans were determined in representative regions of interest. Resected tissue from six ferumoxtran patients and from three patients who did not receive ferumoxtran was assessed for localization of iron in tumour and reactive brain. Results: All malignant tumours (all of which enhanced by gadolinium MR) showed ferumoxtran accumulation with T1 and T2 signal changes, even using a 0.15 T intraoperative MR unit in one patient. Iron staining was predominantly in reactive cells (reactive astrocytes and macrophages) and not tumour cells. In five of the seven patients, including two patients who showed additional lesions, areas enhancing with ferumoxtran but not with gadolinium were observed. Comparison of the pre‐ and postoperative MR revealed residual ferumoxtran‐enhancing areas in four of seven cases. Conclusion: In malignant tumours, ferumoxtran may show areas of enhancement, even with a 0.15 T intraoperative MR, that do not enhance with gadolinium. Ferumoxtran‐enhancing lesions have persistent increased T1 signal intensity for 2–5 days, which may provide advantages over gadolinium for postoperative imaging. Histochemistry for iron shows uptake of ferumoxtran in reactive cells (astrocytes and macrophages) rather than tumour cells.

Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat

Central nervous system (CNS) drainage may occur via connections to the vasculature, but in animal models up to 50% occurs via perivascular, perineural and primitive lymphatic drainage to cervical lymph nodes. We evaluated efflux of particles from the brain to cervical lymph nodes in normal rats, using Combidex iron oxide‐based magnetic resonance imaging (MRI) agent. After intracerebral, intraventricular, intracarotid or intravenous injection of Combidex in normal Long Evans rats, particle localization was assessed by MRI and histochemistry for iron and the dextran coat (n = 27). Intraventricular or intracerebral injection, but not intracarotid administration of Combidex (100 µg), resulted in MRI signal changes in the deep cervical lymph nodes around the carotid artery, and, less strongly, in the superficial cervical nodes. Within 2 h of Combidex administration, iron was histologically localized in cervical lymph nodes, with patched staining of capsule and peripheral sinus consistent with delivery via multiple afferent lymphatic vessels. Lymph node staining in groups receiving CNS Combidex was significantly different from controls (P < 0.0001) and was significantly localized in the deep vs. superficial cervical lymph nodes (P = 0.0003). The trafficking of the superparamagnetic iron particles from the CNS in the rat could be visualized by MRI and histology. Combidex provides a powerful tool to rapidly assess drainage of virus‐sized particles from the CNS.

Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate gadoteridol enhancement in high grade gliomas

Delayed ferumoxytol enhancement on T1‐weighted images appears visually similar to gadoteridol enhancement. The purpose of this study was to quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with an objective, semi‐automated method.

Cerebral blood volume mapping with ferumoxytol in dynamic susceptibility contrast perfusion MRI: Comparison to standard of care: Ferumoxytol Brain DSC Perfusion MRI

Cerebral blood volume (CBV) mapping with a dynamic susceptibility contrast (DSC) perfusion technique has become a clinical tool in diagnosing and follow‐up of brain tumors. Ferumoxytol, a long‐circulating iron oxide nanoparticle, has been tested for CBV mapping, but the optimal dose has not been established.

Spinal Cord Herniation: Why Anterior Thoracic?

Background: Spinal cord herniation and thoracic anterior adhesion syndrome make up the two extremes of a rare condition; characterized by anterior dural adhesion or protrusion of the spinal cord through the arachnoideal and dural membrane into the extradural space, respectively. Summary: We present the main features of the condition by our case series and forward a hypothesis for the consistent anterior, mid-thoracic localization. We surmise the role of an anterior pulling force by the Hofmann (meningo-vertebral) ligaments; acting when the physiologic thoracic kyphosis suddenly increases. The traction may tear the anterior dura; resulting in a dural defect; it allows the nipping/ protrusion of the spinal cord. Key messages: Because the spinal cord compression syndrome caused by adhesion or herniation of the spinal cord may be surgically treatable; the recognition of the condition is essential. The pathogenetic traction effect of the Hofmann ligament in the affected level may have surgical an prognostic implications.