T2-relaxometry predicts outcome of DBS in idiopathic Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) nowadays is a well-established treatment of motor symptoms in Parkinson's disease. The subthalamic nucleus (STN) is a common target for DBS, because motor improvements have been shown to be superior to best medical therapy, if DBS electrodes have been appropriately positioned. DBS target identification can be assisted by MRI beyond structural imaging by spatially resolved measurement of T2-relaxation times (T2r). AIM: We pose the question, whether T2r of the STN is linked to the severity of the disease and whether outcome of DBS may be correlated to an asymmetric manifestation of the disease. Further, we investigated if abnormal T2r in the STN may be predictive for outcome of DBS. METHODS: Twelve patients underwent preoperative MR imaging including a multi echo relaxometry sequence (3 Tesla, Siemens Medical Systems, Erlangen, Germany) ahead of DBS. T2r were determined for STN, substantia nigra (SN), red nucleus (RN) and centrum semiovale (CSO). Unified Parkinson's disease Rating Scale (UPDRS) scores were tested before and after DBS. Patients' T2r and deduced values representing left-right asymmetry of measurements were correlated with UPDRS scores and measures for outcome of DBS. Furthermore, patients' T2r were compared with T2r measurements in 12 healthy controls (HC). RESULTS: Patients' T2r for SN (mean 45.4 ms ± 4.4 ms) and STN (mean 56.4 ms ± 3.8 ms) were significantly shorter than T2r in HCs for SN (mean 60.7 ± 4.6) and STN (mean 66.1 ms ± 4.0 ms). While no mean T2r asymmetry was found in the SN, patients' mean T2r for STN showed a weakened left-right correlation (Pearson correlation coefficient 0.19 versus 0.72 in HC) indicating asymmetric degeneration. T2r asymmetry was not linked to the more severely affected hemisphere. The respective lower T2r within the left or right target region was significantly correlated to the outcome in terms of UPDRS III improvement in "off" state (Pearson correlation 0.82 corresponding to p â‰ª 0.01). Patients with T2r of STN lower than 50 ms showed no response to DBS in the UPDRS. The maximum T2r for SN correlated to the improvement between UPDRS "off" minus and "on" (Dopamine response) but failed to predict DBS outcome. CONCLUSIONS: The lower boundaries of T2r in the STN predict motor outcome in DBS. T2r asymmetry in the STN is not associated with increased clinical symptoms, but with response to therapy. Thus, patients with very low T2r may be inappropriate candidates for DBS.

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study.

BACKGROUND: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. METHODS: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. RESULTS: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 µg/mL to 25 µg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. CONCLUSION: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.