ABSTRACT
This work reports results of experiments in hollow-fiber bioreactor C6 glioma cell cultures where the apparent diffusion coefficient (ADC) of intracellular water (iADC) was measured at diffusion times between 0.83 and 40 ms. The experiments were carried out before and after the onset of permanent ischemia. The changes in iADC following ischemia were dependent on the diffusion time employed in the experiment. An ischemia-induced decrease in the iADC was measured at short diffusion times, while at long diffusion times the iADC increased. Decreases in the iADC measured at short diffusion times are interpreted to be a result of a decrease in the intrinsic diffusivity of intracellular water due to energy failure. Increases in iADC measured at long diffusion times, are interpreted to result from cell swelling.
Subject(s)
Body Water/metabolism , Brain Ischemia/metabolism , Brain Neoplasms/metabolism , Diffusion Magnetic Resonance Imaging/methods , Glioma/metabolism , Animals , Bioreactors , Cell Hypoxia , Cell Line, Tumor , Contrast Media/administration & dosage , Gadolinium DTPA/administration & dosage , Intracellular Fluid/metabolism , Magnetic Resonance Angiography/methods , Magnetic Resonance Spectroscopy/methods , Rats , Tumor Cells, CulturedABSTRACT
Diffusion-weighted MRI is commonly used in the diagnosis and evaluation of ischemic stroke because of the rapid decrease observed in the apparent diffusion coefficient (ADC) of tissue water following ischemia. Although this observation has been clinically useful for many years, the biophysical mechanisms underlying the reduction of tissue ADC are still unknown. To help elucidate these mechanisms, we have employed a novel three-dimensional (3D) hollow-fiber bioreactor (HFBR) perfused cell culture system that enables cells to be grown to high density and studied via MRI and MRS. By infusing contrast media into the HFBR, signals from intracellular water and extracellular water are spectroscopically resolved and can be investigated individually. Diffusion measurements carried out on C6 glioma HFBR cell cultures indicate that ischemia-induced cellular swelling results in an increase in the ADC of intracellular water from 0.35 microm(2)/ms to approximately 0.5 microm(2)/ms (diffusion time = 25 ms).
Subject(s)
Body Water/chemistry , Brain Ischemia/metabolism , Brain Neoplasms/metabolism , Glioma/metabolism , Magnetic Resonance Spectroscopy/methods , Oxygen/metabolism , Water/analysis , Animals , Body Water/metabolism , Brain Ischemia/diagnosis , Cell Hypoxia , Cell Line, Tumor , Diffusion , RatsABSTRACT
The complexity of biologic tissues, with multiple compartments each with its own diffusion and relaxation properties, requires complex formalisms to model water signal in most magnetic resonance imaging or magnetic resonance spectroscopy experiments. In this article, we describe a magnetic susceptibility-induced shift in the resonance frequency of extracellular water by the introduction of a gadolinium contrast agent to medium perfusing a hollow fiber bioreactor. The frequency shift of the extracellular water (+185 Hz at 9.4 T) uncovers the intracellular water and allows direct measurement of motional and relaxation properties of the intracellular space. The proposed method provides a unique tool for understanding the mechanisms underlining diffusion and relaxation in the intracellular space.
