Time Domian Electron Paramagnetic Resonance Imaging

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Goals and Objectives: The goals of this project are to develop instrumentation, concepts in imaging physics and image reconstruction to provide the ability to non-invasively image properties associated tumor physiology such as tumor oxygenation, tumor microvessel density and tumor blood flow. Using such capabilities, we propose to use them to longitudinally monitor changes in tumor physiology in response to tumor growth, treatment with chemotherapeutic agents and ionizing radiation and the combination. Such capabilities will make it possible to identify temporal profiles of changes in these factors to optimize treatment. Of the various imaging modalities available to determine these properties pertaining to tumor physiology, Electron Paramagnetic Resonance Imaging (EPRI) using paramagnetic tracers has a unique ability to quantitatively provide such information and can be used serially during the tumor growth and also treatment phase. This capability enables monitoring changes in tumor oxygen status in response to treatments such as chemotherapy, anti-angiogenic drug therapy, and radiotherapy and correlate such information with anatomic images and information pertaining to blood vessel density and blood flow. The specific goals of this project are summarized below: 1) Develop and optimize EPR Imaging instrumentation for small animal imaging with capabilities to image tissue oxygen concentration with a spatial resolution of < 2 mm in an imaging time of ~2 minutes with a pO2 discriminating capability of +/- 3 mm Hg. 2) Develop imaging algorithms improving temporal, spectral (Physiologic) and spatial resolution and co-register the images with those from MRI and also additional physiologic information such as tumor blood vessel density, blood flow, and metabolic profile. 3) Develop image formation methods capable of serially monitoring changes in tumor oxygen status, physiology, and metabolic status in response to treatment. 4) Evaluate strategies to scale up this modality for human applications. Project Summary: A novel split patch antenna and saddle coil resonant structure for EPR Imaging: EPR imaging capabilities have been demonstrated to percform pO2 imagingin small animal such as mice to study the tumor microenvironment in terms of physiology in mouse models of human cancers. The unique capabilities of EPR to quantitatively map tumor pO2 and also dynamically monitor changes have been demonstrated. With the availability of novel trityl probe such as Oxo71 which is well tolerated at doses needed for imaging and its capability to report on tissue oxygen from normoxic to hypoxic regions has motivated the development of an imaging system to probe larger sized objects and eventually in humans. The current resonant structures available can study small animals such as mice.For larger sized objects novel resnonant structures need to be explored while keeping the requirements such as RF bandwidths in the range of 30 MHz, efficient RF to B1 conversion and sub-microsecond recovery after RF excitation. We have developed a patch antenna transmitter and a saddle coil resonator with optimized Q and bandwidth was used to perform EPR imaging in time-domain to cover a phantom of large volume as prelude to in vivo functional EPR imaging to open up possibilities of scaling up of EPR imaging to practically useful in cancer research and tissue oximetry. A 60 mm diameter x 110 mm length resonant structure was built to operate at 300 MHz with a resonator recovery time of < 600 ns and a bandwidth of 20 MHz. A phantom object comprised of several tubes containing the paramagnetic system in aqueous media distributed over volume of 7.5 X 7.5 X 7.5 cm was imaged. Images of phantom object comprised of several tubes filled with trityl radical showed that this concept is feasible for EPR imaging of large objects where the spin dynamics are in the microsecond time range. This resonant structure is implemented for the first time with sufficient bandwidth and short recovery time to image signals from a large volume resonator. This design allows easy scale up for human size objects. Evaluation of renal hypoxia in cisplatin-induced chronic kidney disease. Cisplatin treatment is associated with kidney injury and chronic kidney disease. In this study, we used EPR Imaging to. Map kidney pO2 and changes when treated with cisplatin. Quantitative oxygen imaging by EPR revealed a striking decrease in pO2 with cisplatin treatment. This decrease. Is correlated by accompanied increase in protein levels of fibronectin and a-SMA which are associated with fibrosis. These studies suggest that cicplatin treatment can be associated with chronic kidney disease. The results further demonstrate the capability of EPR to non-invasively monitor renal physiology. Such capabilities can aid in the management of mitigating strategies of kidney damage associated with chemotherapy. Similar studies have been done on the effect of cyclophosphamide on renal physiology. This study evaluated Electron Paramagnetic Resonance (EPR)-based oxygen imaging using the paramagnetic tracer Ox071 to assess kidney oxygen levels in mice with cyclophosphamide-induced kidney injury. Urine pO2 was also assessed as a potential surrogate marker. EPR oximetry accurately measured kidney oxygen distribution, revealing a temporary increase in pO2 post-injury. Urine oximetry, however, did not reliably reflect changes in kidney oxygenation. Overall our studies have demonstrated the capabilituy of EPR based pO2 imaging as a promising, non-invasive tool for monitoring renal oxygenation, offering high-resolution mapping and longitudinal assessment. Its ability to provide detailed information about oxygen distribution within the kidney makes it a valuable tool for studying the pathophysiology of renal diseases and for developing novel therapeutic strategies.