Theory, Instrumentation, and Applications of Electron Paramagnetic Resonance Oximetry

Ahmad, Rizwan; Kuppusamy, Periannan

doi:10.1021/cr900396q

Cited by 133 publications

(129 citation statements)

References 232 publications

(390 reference statements)

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…[20][21][22][23] Confirmation of 23,31 Of note, although this paper focuses on longitudinal WM changes, it will be of interest to determine differences, if any, between WM compared with graymatter pO 2 in the SHR/SP model using EPR oximetry in future endeavors. We measured pO 2 in the WM of SHR/SP at 6 weeks of age before the onset of severe hypertension; all of the animals in the three groups showed similar levels of pO 2 up to 12 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…Electron paramagnetic resonance oximetry allows for repetitive and highly accurate measurement of localized tissue pO 2 ; 20 thus, it is a novel and innovative method for interstitial pO 2 measurement in living animals and has proven to be an important tool in the study of brain tissue pO 2 . [20][21][22][23] Briefly, molecular O 2 , being paramagnetic, broadens the EPR spectral lines of other paramagnetic species, or paramagnetic probes. 20 Measured changes in EPR spectral linewidth have been used to estimate O 2 and recently, localized cerebral interstitial pO 2 can be monitored and characterized at a single specific site in vivo using stable paramagnetic lithium phthalocyanine (LiPc) particles.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

Weaver

Jalal

Yang

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O 2 is critical in brain physiology, tissue O 2 level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO 2 ) in the deep WM. We tested this hypothesis by monitoring WM tissue pO 2 using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO 2 from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO 2 to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO 2 was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO 2 may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO 2 in the WM of small animals. Keywords: brain oxygen; EPR oximetry; vascular cognitive impairment; white matter INTRODUCTION Brain cells poorly tolerate hypoxia, and even short periods of low oxygen (O 2 ) can initiate molecular pathways that are lethal to cells in both the gray and white matter (WM). Deep WM is a common site of hypoxic/ischemic injury in the elderly where it is associated with cognitive decline, gait disturbances, and focal ischemia leading to vascular cognitive impairment (VCI). Magnetic resonance imaging (MRI) reveals white-matter hyperintensities (WMHs) in the elderly located in the periventricular and subcortical regions, and considered to be due to strokes and secondary small vessel disease. An alternative mechanism is that the deep WM is vulnerable to hypoxia for a variety of reasons. Studies in humans suggest that there is impairment in the ability of the deep WM to respond to increased demand by raising cerebral blood flow or O 2 . 1 Although glutamate mediated excitotoxicity, inflammatory cytokines, and protease activation result in oligodendrocyte death in acute ischemic injury, the pathophysiology of WM injury in chronic vascular disease has not been fully explored. 2 Small vessel disease is associated with WMHs in patients with VCI; damage to small vessels causes an inflammatory response with disruption in the blood-brain barrier (BBB) associated with expression of matrix metalloproteinases (MMPs) and subsequent damage to the WM. Vascular dementia patients show expression of MMPs in regions of loss of myelin. [3][4][5]

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

Weaver

Jalal

Yang

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…However, trityl radicals are known to be difficult to prepare, and we present herein protocols that worked reproducibly in our hands for known and new derivatives. The synthesis of tetrathia-TAM radicals is shown in Scheme 1. iii 4: R 1 = CH 3 , R 2 = COOCH 2 CH 3 5: R 1 = CH 3 , R 2 = COOC(CH 3 ) 3 6: R 1 = CD 3 , R 2 = COOC(CH 3 ) 3 iv for 9 7: R 1 = CH 3 , R 2 = COOCH 2 CH 3 8: R 1 = CH 3 , R 2 = COOC(CH 3 ) 3 9: R 1 = CD 3 , R 2 = COOH 10: R 1 = CH 3 , R 2 = COOH 11: R 1 = CD 3 , R 2 = COOCH 2 CH 3 (via v) 12: R 1 = CD 3 , R 2 = COCl (via vi) 13: R 1 = CD 3 , R 2 = COOCD 2 CD 3 (via vii or viii) v -viii Scheme 1. Synthesis of tetrathia-TAM radicals 7-13.…”

Section: Synthesis Of Tetrathia-tam Radicals Their Deuterated Analogmentioning

confidence: 99%

Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors

et al. 2015

View full text Add to dashboard Cite

Tissue oxygenation plays an important role in the pathophysiology of various diseases and is often a marker of prognosis and therapeutic response. EPR (ESR) is a suitable noninvasive oximetry technique. However, to reliably deploy soluble EPR probes as oxygen sensors in complex biological systems, there is still a need to investigate and improve their specificity, sensitivity, and stability. We reproducibly synthesized various derivatives of tetrathiatriarylmethyl and tetrachlorotriarylmethyl (trityl) radicals. Hydrophilic radicals were investigated in aqueous solution mimicking physiological conditions by, e.g., variation of viscosity and ionic strength. Their specificity was satisfactory, but the oxygen sensitivity was low. To enhance the capability of trityl radicals as oxygen sensors, encapsulation into oily core nanocapsules was performed. Thus, different lipophilic triesters were prepared and characterized in oily solution employing oils typically used in drug formulations, i.e., middle-chain triglycerides and isopropyl myristate. Our screening identified the deuterated ethyl ester of D-TAM (radical 13) to be suitable. It had an extremely narrow single EPR line under anoxic conditions and excellent oxygen sensitivity. After encapsulation, it retained its oxygen responsiveness and was protected against reduction by ascorbic acid. These biocompatible and highly sensitive nanosensors offer great potential for future EPR oximetry applications in preclinical research.

show abstract

“…While currently it is mostly limited to the preclinical setting [22], some works have extended it to clinical use [23,24]. This technique, called ESR oximetry, requires the incorporation of a suitable stable paramagnetic spin probe into the desirable sample.…”

Section: Introductionmentioning

confidence: 99%

Electron spin resonance microscopic imaging of oxygen concentration in cancer spheroids

Hashem

Weiler-Sagie

Kuppusamy

et al. 2015

Journal of Magnetic Resonance

Self Cite

View full text Add to dashboard Cite

Theory, Instrumentation, and Applications of Electron Paramagnetic Resonance Oximetry

Cited by 133 publications

References 232 publications

Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors

Electron spin resonance microscopic imaging of oxygen concentration in cancer spheroids

Contact Info

Product

Resources

About