Can the Discovery of High-Impact Diagnostics Be Improved by Matching the Sampling Rate of Clinical Diagnostics to the Frequency Domain of Diagnostic Information?

Authors

Steven W Millward
Peng Wei
David Piwnica-Worms
Seth T Gammon

Publication Date

4-22-2025

Journal

Cancers

Abstract

Over the past 30 years, academic and industrial research investigators have developed molecular reporters to visualize cell death in complex biological systems. In parallel, clinical researchers, chemists, biochemists, and molecular biologists have endeavored to translate these molecular tools into clinical imaging agents. Despite these efforts, there are no clinically approved imaging methodologies with which to image cell death consistently and quantitatively. One reason may reside in the intrinsic mismatch between the sampling frequency of translational molecular imaging and the biochemical kinetics that define cell death. Beyond cell death imaging, many active research programs are now attempting to create translational diagnostic pharmaceuticals to image immunological, fibrotic, amyloidotic, and metabolic pathways. Each of these pathways is defined by a unique set of biochemical rate constants, some of which are associated with key predictive pathways. Exhaustively sampling all permutations of pathways and kinetic constants would seem to be an intractable strategy for target identification and validation. Sampling theory, if applied to these pathways, could accelerate the translation of high-impact diagnostics through prioritization of pathways for either AI enhanced diagnostic imaging or AI-enhanced wearable devices. In this perspective, we identify the Nyquist sampling rate as a key criterion for evaluating the optimal application for novel diagnostics. Sampling theory states that to fully characterize a band-limited, stationary, temporal data set, the signal must be sampled at more than twice the rate of the fastest frequency in the signal or, for diagnostics, the discriminatory signal. Through the study of the medical imaging process chain, Nyquist sampling rates of 0.25 day

Keywords

cell death, diagnostic imaging, drug development, fourier analysis, inflammation imaging, multi-resolution analysis, product development

DOI

10.3390/cancers17091387

PMID

40361314

PMCID

PMC12071022

PubMedCentral® Posted Date

4-22-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes