Pilot study on high-resolution radiological methods for the analysis of cerebrospinal fluid (CSF) shunt valves.

OBJECTIVES: Despite their life-saving capabilities, cerebrospinal fluid (CSF) shunts exhibit high failure rates, with a large fraction of failures attributed to the regulating valve. Due to a lack of methods for the detailed analysis of valve malfunctions, failure mechanisms are not well understood, and valves often have to be surgically explanted on the mere suspicion of malfunction. The presented pilot study aims to demonstrate radiological methods for comprehensive analysis of CSF shunt valves, considering both the potential for failure analysis in design optimization, and for future clinical in-vivo application to reduce the number of required shunt revision surgeries. The proposed method could also be utilized to develop and support in situ repair methods (e.g. by lysis or ultrasound) of malfunctioning CSF shunt valves. MATERIALS AND METHODS: The primary methods described are contrast-enhanced radiographic time series of CSF shunt valves, taken in a favorable projection geometry at low radiation dose, and the machine-learning-based diagnosis of CSF shunt valve obstructions. Complimentarily, we investigate CT-based methods capable of providing accurate ground truth for the training of such diagnostic tools. Using simulated test and training data, the performance of the machine-learning diagnostics in identifying and localizing obstructions within a shunt valve is evaluated regarding per-pixel sensitivity and specificity, the Dice similarity coefficient, and the false positive rate in the case of obstruction free test samples. RESULTS: Contrast enhanced subtraction radiography allows high-resolution, time-resolved, low-dose analysis of fluid transport in CSF shunt valves. Complementarily, photon-counting micro-CT allows to investigate valve obstruction mechanisms in detail, and to generate valid ground truth for machine learning-based diagnostics. Machine-learning-based detection of valve obstructions in simulated radiographies shows promising results, with a per-pixel sensitivity >70%, per-pixel specificity >90%, a median Dice coefficient >0.8 and <10% false positives at a detection threshold of 0.5. CONCLUSIONS: This ex-vivo study demonstrates obstruction detection in cerebro-spinal fluid shunt valves, combining radiological methods with machine learning under conditions compatible to future in-vivo application. Results indicate that high-resolution contrast-enhanced subtraction radiography, possibly including time-series data, combined with machine-learning image analysis, has the potential to strongly improve the diagnostics of CSF shunt valve failures. The presented method is in principle suitable for in-vivo application, considering both measurement geometry and radiological dose. Further research is needed to validate these results on real-world data and to refine the employed methods. In combination, the presented methods enable comprehensive analysis of valve failure mechanisms, paving the way for improved product development and clinical diagnostics of CSF shunt valves.

Quasi-continuous production of highly hyperpolarized carbon-13 contrast agents every 15 seconds within an MRI system.

Hyperpolarized contrast agents (HyCAs) have enabled unprecedented magnetic resonance imaging (MRI) of metabolism and pH in vivo. Producing HyCAs with currently available methods, however, is typically time and cost intensive. Here, we show virtually-continuous production of HyCAs using parahydrogen-induced polarization (PHIP), without stand-alone polarizer, but using a system integrated in an MRI instead. Polarization of ≈2% for [1-13C]succinate-d2 or ≈19% for hydroxyethyl-[1-13C]propionate-d3 was created every 15 s, for which fast, effective, and well-synchronized cycling of chemicals and reactions in conjunction with efficient spin-order transfer was key. We addressed these challenges using a dedicated, high-pressure, high-temperature reactor with integrated water-based heating and a setup operated via the MRI pulse program. As PHIP of several biologically relevant HyCAs has recently been described, this Rapid-PHIP technique promises fast preclinical studies, repeated administration or continuous infusion within a single lifetime of the agent, as well as a prolonged window for observation with signal averaging and dynamic monitoring of metabolic alterations.

Microglial CX3CR1 promotes adult neurogenesis by inhibiting Sirt 1/p65 signaling independent of CX3CL1.

Homo and heterozygote cx3cr1 mutant mice, which harbor a green fluorescent protein (EGFP) in their cx3cr1 loci, represent a widely used animal model to study microglia and peripheral myeloid cells. Here we report that microglia in the dentate gyrus (DG) of cx3cr1 (-/-) mice displayed elevated microglial sirtuin 1 (SIRT1) expression levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 activation, despite unaltered morphology when compared to cx3cr1 (+/-) or cx3cr1 (+/+) controls. This phenotype was restricted to the DG and accompanied by reduced adult neurogenesis in cx3cr1 (-/-) mice. Remarkably, adult neurogenesis was not affected by the lack of the CX3CR1-ligand, fractalkine (CX3CL1). Mechanistically, pharmacological activation of SIRT1 improved adult neurogenesis in the DG together with an enhanced performance of cx3cr1 (-/-) mice in a hippocampus-dependent learning and memory task. The reverse condition was induced when SIRT1 was inhibited in cx3cr1 (-/-) mice, causing reduced adult neurogenesis and lowered hippocampal cognitive abilities. In conclusion, our data indicate that deletion of CX3CR1 from microglia under resting conditions modifies brain areas with elevated cellular turnover independent of CX3CL1.

Dental MRI: imaging of soft and solid components without ionizing radiation.

PURPOSE: To evaluate the ability of conventional and ultra-short or zero echo time MRI for imaging of soft and solid dental components in and ex vivo. MATERIALS AND METHODS: Turbo spin echo (TSE), ultra-short echo time (UTE), and zero echo time (ZTE) MRI were performed on extracted (human and equine) teeth and in vivo using whole-body and small-bore MR systems at 3 T, 7T, and 9.4T, respectively. RESULTS: At an isotropic resolution of (600 µm)(3) , strong signal of soft-tissue, e.g., mucosa and nerves with excellent contrast was achieved using TSE at 3T in vivo. No signal, though, was obtained from solid components, e.g., teeth (due to short T(2) ). In contrast, dentin, cementum as well as enamel of extracted teeth were readily depicted using UTE and ZTE at a resolution of ≈ (150 µm)(3) at 7T and 9.4T. In particular, ZTE provided higher signal in enamel. CONCLUSION: As an alternative to X-ray based methods like cone-beam computed tomography (CT) or conventional CT, the presented results demonstrate the potential of ZTE and UTE MRI as a radiation-free imaging modality, delivering contrast of soft and solid components at the same time.

On-chip three dimensional microcoils for MRI at the microscale.

We present for the first time a fully MEMS-integrated technology to manufacture 3D geometrically perfect solenoidal microcoils for microscale MRI applications. We report 25 microm isotropic resolution MR images of a copper sulfate aqueous phantom. These images are acquired using microcoils with 5 windings of insulated 25 microm diameter Au wire and with quality factors as high as 46 at the operating frequency (400 MHz).

Diffusion-weighted imaging as predictor of therapy response in an animal model of Ewing sarcoma.

OBJECTIVES: To evaluate the potential of diffusion-weighted imaging (DWI) for monitoring dose-dependent tumor response in a mouse-xenograft model of Ewing sarcoma after administration of treosulfan in different dosages. MATERIALS AND METHODS: Ewing sarcoma implanted orthotopically into the left thigh of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice were evaluated with a 9.4 T MR unit by using a specific mouse whole body coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin-echo sequences, and transverse echo-planar DWI examinations were performed at baseline, 24 hours and 72 hours after intraperitoneal injection of treosulfan in 2 different doses. The apparent diffusion coefficient (ADC) in the viable parts of the tumor was automatically calculated from DWI imaging findings. These findings were correlated with histopathologic results at each time point. Volumetric measurements were performed by summing up the regions of interest in consecutive slices. RESULTS: T1- and T2-weighted images before administration of treosulfan showed viable tumor tissue with small necrotic areas. At 24 hours after treosulfan injection, a significantly higher increase in ADC in the viable parts of the tumor could be observed in tumors of mice that had been injected with the higher dose of treosulfan compared with mice injected with the lower dose treosulfan, whereas no significant volumetric differences between the 2 different doses could be observed. Seventy-two hours after injection of treosulfan the ADC values in the viable parts of the tumor of mice treated with the high dose of treosulfan further increased and the tumor volume in the high-dose group was now significantly lower than in the low-dose group. CONCLUSION: Compared with volumetric measurements, DWI of the viable tumor parts could be used to discriminate between the effects of 2 different dosages at an earlier time point than volumetric measurements in an animal model in vivo. This method could be especially useful for monitoring drug effects in phase I/II clinical trials.