Advanced Imaging Methods in Pulse EPR

Abstract: Precise partial oxygen pressure (pO2) measurements can guide therapeutic intervention in cancer and other fields. Pulse electron paramagnetic resonance imaging (pEPRI) is an outstanding method for imaging pO2 using the linear relationship between spin-lattice relaxation rate R1 (=1/T1) and pO2 using an oxygen-sensitive trityl OXO71 as the contrast agent. Usually, T1 is extracted from an inversion recovery electron spin echo (IRESE) combined with the radial acquisition imaging method. For IRESE, multiple experiments with different delays have to be performed to capture T1-dependent spin evolution. Additionally, the IRESE imaging method requires high RF power for pi-pulses, which makes it poorly scalable to larger objects and higher resolutions. Another technique, single point imaging (SPI), offers higher resolution and requires lower power but is slow and inefficient in T1 imaging. To resolve this issue and to obtain fast and precise pO2 imaging using pEPRI, we have taken inspiration from magnetic resonance fingerprinting (MRF) and invented a pulse EPR Fingerprinting (EPRF) method combined with the SPI acquisition strategy, named single point fingerprinting (SPF) imaging. The SPF method utilizes a sequence of many pulses followed by signal detection after each of them. The overall duration of the pulse sequence is comparable to the T1 relaxation time, thus forming a non-equilibrium acquisition strategy. The relaxation times are extracted by matching experimental traces to a dictionary obtained from the Bloch equation simulations of spin systems with different T1 and T2, corresponding to a pO2 value and B1. In Aim One, we will establish the hardware to implement variable flip-angle sequences with bandwidth- compensated pulses; in Aim Two, we will develop the SPF sequences and dictionary for SPF; Aim Three will evaluate SPF with phantom experiments and with proof of concept in vivo study of fibrosarcoma and head and neck tumor models, thus covering a range of hypoxia; Aim Four will assess an early response of radiotherapy using SPF with a hypoxic 4T1 and a normoxic MCF-7 mouse tumor models, while also comparing the efficiency of SPF with IRESE for animals breathing medical grade air (21% O2) and 100 % O2, thus covering a broad range of pO2. The technique developed in this project is expected to increase the speed and spatial resolution of oxygen imaging while reducing the RF power needed for imaging, thus making pO2 EPR imaging translatable to clinics. The long-term goal of this project is to utilize pEPRI in clinical oximetry applications, where it can assist with cancer treatment and evaluation of other pathologies.