Ph Sensor Blood — Biomedical Instrumentation & Clinical Sensing

Abstract — Ph Sensor Blood

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. pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5- 13 C 2 ]Z-OMPD as a hyperpolarized extracellular pH and perfusion sensor for MRI which allows to generate a multiparametric fingerprint of renal disease status and to detect local tumor acidification. Exceptional long T 1 of two minutes at 1 T, high pH sensitivity of up to 1.9 ppm per pH unit and suitability of using the C 1 -label as internal frequency reference enables pH imaging in vivo of three pH compartments in healthy rat kidneys. Spectrally selective targeting of both 13 C-resonances enables simultaneous imaging of perfusion and filtration in 3D and pH in 2D within one minute to quantify renal blood flow, glomerular filtration rates and renal pH in healthy and hydronephrotic kidneys with superior sensitivity compared to clinical routine methods. Imaging multiple biomarkers within a single session renders [1,5- 13 C 2 ]Z-OMPD a promising new hyperpolarized agent for oncology and nephrology.

Sensor Interfacing & Analog Front-End Conditioning

Onco-nephrology is an emerging medical field in the interdisciplinary care of patients to identify and prevent kidney damage or failure related to cancer treatments as well as to assess risk for cancer due to kidney disease 1 , 2 . Upon diagnosis of cancer, state-of-the-art treatment options employ chemo- and radiotherapy. While treatment outcome can be significantly affected by prevailing pH conditions in the tumor 3 , pH-regulating adjuvant therapies 4 might be crucial to enhance patient outcome 5 , as long and ineffective therapies often pose a severe kidney burden 6 . Therefore, for many therapies it might be essential to assess the tumor pH, as well as the renal function before, during and following cancer treatment, for which renal acid-base balance and glomerular filtration rates 7 are important biomarkers. In clinical routine, kidney function is probed by iodinated contrast multiphase CT 8 , 9 or scintigraphy using 99m Tc-MAG3 10 as imaging agent. Recently introduced methods, not translated in clinical routine yet, involve the injection of Gd-based contrast agents for DCE-MRI 11 , diffusion weighting 12 or arterial spin labelling 13 , 14 . However, scintigraphy using 99m Tc-MAG3 involves the injection of ionizing radiation and spin-labelling- and diffusion-weighted-techniques are sensitive to abdominal motion and limit assessment of the complete renal filtration process. Further, CT-based contrast agents can induce nephropathies 15 , which poses a major risk for single or repeated assessment of already fragile kidney conditions, while MRI-based contrast agents can accumulate in organs 16 , bear a risk of inducing nephrogenic systemic fibrosis in patients with impaired kidney function 17 and are suspected to accelerate metastasis 18 . In addition, despite several first studies to image pH in human patients 19 , 20 , 21 , 22 , 23 , there is no routinely applied noninvasive imaging method available yet. These approaches rely on iodine-based injectable CEST-agents for extracellular pH measurements (acidoCEST) 19 , 21 , 22 , 23 or generate only pH- and intracellularly-weighted images using endogenous amide protons for contrast generation (APT-CEST) 20 . Simultaneously, there is a strong clinical need for safe and fast imaging of extracellular pH to assess tumor acidification for patient stratification, efficacy of adjuvant therapies or early response to therapy 24 .

Bio-Signal Waveform Analysis & Simulation Findings

Figure 1: Diagnostic Medical Waveform & Bio-Potential Clinical Trace for Ph Sensor Blood Hyperpolarized magnetic resonance imaging is an imaging technique on the transition to the clinic 25 , which relies on the injection of isotopically enriched, non-toxic contrast agents. Among these, [ 13 C]urea 26 , [ 13 C, 15 N 2 ]urea 27 , [ 13 C]2-Methylpropan-2-ol 28 , HP001 29 and hyperpolarized water 30 have been introduced as perfusion agents. While the latter three have been preclinically investigated for assessment of kidney 27 , 31 , 32 , 33 and tumor 34 perfusion with quantitative assessment of kidney filtration rates 35 , [ 13 C, 15 N 2 ]urea has also been recently translated into clinical trials 36 , 37 .

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