Microdialysis Probe — Biomedical Instrumentation & Clinical Sensing

Abstract — Microdialysis Probe

experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. In order to study metabolic processes in animal models of diseases and in patients, microdialysis probes have evolved as powerful tools that are minimally invasive. However, analyses of microdialysate, performed remotely, do not provide real-time monitoring of microdialysate composition. Microdialysate solutions can theoretically be analyzed online inside a preclicinal or clinical MRI scanner using MRS techniques. Due to low NMR sensitivity, acquisitions of real-time NMR spectra on very small solution volumes (µL) with low metabolite concentrations (mM range) represent a major issue. To address this challenge we introduce the approach of combining a microdialysis probe with a custom-built magnetic resonance microprobe that allows for online metabolic analysis ( 1 H and 13 C) with high sensitivity under continuous flow conditions. This system is mounted inside an MRI scanner and allows performing simultaneously MRI experiments and rapid MRS metabolic analysis of the microdialysate. The feasibility of this approach is demonstrated by analyzing extracellular brain cancer cells (glioma) in vitro and brain metabolites in an animal model in vivo . We expect that our approach is readily translatable into clinical settings and can be used for a better and precise understanding of diseases linked to metabolic dysfunction.

Sensor Interfacing & Analog Front-End Conditioning

Microdialysis is a valuable tool for in vivo investigations and can be placed in many tissues and organs including brain for neurological investigations of Alzheimer 1 , 2 , brain tumors 3 , traumatic brain injuries 4 , neuronal functionality 5 and pharmacokinetics of drugs 6 . In combination with magnetic resonance imaging (MRI), dialysate composition can be directly correlated with anatomical structures or pathological changes seen on MRI 7 , 8 . However, metabolic investigations of the dialysate are currently performed remotely and off-line from the MRI scanner 9 , 10 , 11 , 12 due to the limited online sampling possibilities 13 , 14 . Integrating analytical devices within MRI scanners poses challenges (related to limited space and to magnetic interference), limiting the applications of correlation experiments. Here, we introduce a novel approach of online sampling of tissue dialysate under continuous flow utilizing a high resolution nuclear magnetic resonance (NMR) microprobe, closely coupled to an in vivo microdialysis inside an MRI scanner. We present two microprobes that allow for the online metabolic investigation at physiological concentrations ( 1 H: 1.8 mM lactate in 60 s; 13 C: 10.0 mM 3- 13 C lactate in 100 s).

Bio-Signal Waveform Analysis & Simulation Findings

The applicability of the approach is demonstrated by investigating extracellular metabolites, from in vitro brain cancer cells and from in vivo microdialysate of rat brain. Figure 1: Diagnostic Medical Waveform & Bio-Potential Clinical Trace for Microdialysis Probe Micro-structured NMR/MRS probes have been fabricated in a variety of different geometries 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 and have partly been applied to continuous flow investigations 29 , 30 with solenoidal coils being the most sensitive to date 15 , 16 . Utilizing this fact with the goal of online detection of metabolites at physiological concentrations for in vivo studies, we have constructed two different microprobes with solenoidal geometry: a 1 H-optimized probe tuned at 300 MHz and a 13 C-optimized probe with unprecedented sensitivity tuned at 50 MHz.

Scope & Clinical Applications

• Real-time multi-parameter vital signs telemetry (ECG, Heart Rate, SpO2, Temperature, Respiration)
• Low-noise Analog Front-End (AFE) conditioning with active Driven Right Leg (DRL) 50 Hz cancellation
• Digital signal processing in MATLAB: Pan-Tompkins QRS detection, FIR/IIR notch, and Continuous Wavelet Transforms
• Finite element tissue bio-electromagnetics and orthopedic mechanical simulations in COMSOL & ANSYS
• Complete Arduino firmware .INO sketches, circuit schematics, and university dissertation reports