Hyperpolarized 129Xe Magnetic Resonance Spectroscopy in a Rat Model of Bronchopulmonary Dysplasia

Author(s):  
Jordan David Fliss ◽  
Brandon Zanette ◽  
Yonni Friedlander ◽  
Siddharth Sadanand ◽  
Andras A Lindenmaier ◽  
...  

Premature infants often require mechanical ventilation and oxygen therapy which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a non-invasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the Model of Xenon Exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert Hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for non-invasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (L­m), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (tx), were compared with airspace mean axis length and area density (MAL and ρ­A) and percentage area of tissue and air (PTA and PAA) from histology. L­m was significantly larger in the exposed rats (p=0.003) and correlated with MAL, ρ­A, PTA, and PAA (0.59<|ρ|<0.66 and p<0.05). Observed increase in HCT (p=0.012) and changes in tx are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

2021 ◽  
Author(s):  
Hiroki Ohta ◽  
Nhat-Minh Van Vo ◽  
Junichi Hata ◽  
Koshiro Terawaki ◽  
Takako Shirakawa ◽  
...  

Abstract IntroductionAcute compartment syndrome (ACS) leads to a series of health problems, limb salvage, disability, and even death. In vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) provides a unique non-invasive method to assess skeletal muscle metabolisms such as inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate (ATP). The study aims to assess the ability of dynamic 31P-MRS in the early detection of muscular damage in ACS.Materials & MethodsThe study induced the fastened zip-tie model of ACS on normotensive Sprague-Dawley rats (n = 6). The spectra were acquired in Bruker 9.4-Tesla preclinical scanner using 1H/31P surface coil. 31P-MRS spectra and blood samples were obtained at time 0 (pre-ischemic phase) and every 15 minutes during the compression (120 minutes) and the reperfusion phase (90 minutes). 31P-MRS spectra findings were compared with plasma creatine phosphokinase (CPK).ResultsPCr/(Pi + PCr) ratio significantly decreased after muscle was compressed (P < 0.05). In contrast to this, CPK did not change significantly (P > 0.05). Both intracellular pH and arterial pH decreased over time. However, intracellular declined significantly (P < 0.05) at 60 minutes of ischemic state, and at 5 minutes and 60 minutes of reperfusion, while arterial pH slightly changed. After 30 minutes of ischemic, phosphomonoesters (PME) peak was detected, which was not seen at the pre-ischemic phase. It gradually increased and reached its highest peak at 120 minutes. At reperfusion state, 31P-MRS spectra and pH did not fully recover to their pre-ischemic state, and PME peak disappeared. There was a correlation between T2-weighted images and CPK from blood tests (R2 = 0.1996, P < 0.05).ConclusionsDynamic 31P-MRS technique is more clearly and rapidly detect the bioenergetic and mitochondrial functions change than blood test in a fastened zip-tie rat model of ACS. This technique is a promising non-invasive method to detect the early ischemic muscular damage in ACS.


1995 ◽  
Vol 86 (3) ◽  
pp. 329-332 ◽  
Author(s):  
Masafumi Harada ◽  
Miki Tanouchi ◽  
Hiromu Nishitani ◽  
Hirokazu Miyoshi ◽  
Kazuhiko Bandou ◽  
...  

2012 ◽  
Vol 43 (3) ◽  
pp. 431-442
Author(s):  
Stanislava Nagyová ◽  
Mária Kovaľaková ◽  
Oľga Fričová ◽  
Viktor Hronský ◽  
Dušan Olčák ◽  
...  

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.


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