Magnetic Resonance Imaging and Spectroscopy of the Rat Hippocampus 1 Month after Exposure to 56Fe-Particle Radiation

Abstract Obenaus, A., Huang, L., Smith, A., Favre, C. J., Nelson, G. and Kendall, E. Magnetic Resonance Imaging and Spectroscopy of the Rat Hippocampus 1 Month after Exposure to 56Fe-Particle Radiation. Radiat. Res. 169, 149–161 (2008). The response of the central nervous system to space radiation is largely unknown. The hippocampus, which is known for its critical role in learning and memory, was evaluated for its response to heavy-ion radiation. At 1 month, animals exposed to brain-only 56Fe-particle irradiation (0–4 Gy) were examined using contrast-enhanced T1 imaging (CET1), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and 1H-magnetic resonance spectroscopy (MRS). Correlative histology was performed after imaging. The T2WI, DWI and CET1 images revealed no overt anatomical changes after irradiation. Quantitative analysis demonstrated a significant increase in T2 at 2 Gy compared to 0 Gy. The apparent diffusion coefficient (ADC) revealed an inverse dose-dependent quantitative change in water mobility. Compared to 0 Gy, the ADC increased 122% at 1 Gy and declined to 44% above control levels at 4 Gy. MRS showed a significant increase in the N-acetylaspartate/choline ratio at 4 Gy and a lactate peak. Histology demonstrated no overt pathological changes in neuronal and astrocyte populations. However, a significant inverse dose-dependent morphological change in the microglial population was detected in irradiated animals. Our results suggest that early tissue matrix modifications induced by 56Fe-particle radiation can be detected by MRI in the absence of evident histopathology. These changes may indicate fundamental changes in the structure and function of the hippocampus.

[1]  S. Heiland,et al.  Dose–Response Curves and Tolerance Doses for Late Functional Changes in the Normal Rat Brain after Stereotactic Radiosurgery Evaluated by Magnetic Resonance Imaging: Influence of End Points and Follow-up Time , 2002, Radiation research.

[2]  J. Moffett,et al.  Regulation of N‐acetylaspartate and N‐acetylaspartylglutamate biosynthesis by protein kinase activators , 2006, Journal of neurochemistry.

[3]  F. Bova,et al.  Temporal characteristics of radiosurgical lesions in an animal model. , 1994, Journal of neurosurgery.

[4]  W. J. Lorenz,et al.  Dose-response relationship for late functional changes in the rat brain after radiosurgery evaluated by magnetic resonance imaging. , 1997, International journal of radiation oncology, biology, physics.

[5]  F. Bova,et al.  LINAC radiosurgery: an animal model. , 1993, Journal of neurosurgery.

[6]  J. Coyle,et al.  Evidence for the presence of N-acetylaspartylglutamate in cultured oligodendrocytes and LPS activated microglia , 1998, Brain Research.

[7]  B. Shukitt-Hale,et al.  Cognitive deficits induced by 56Fe radiation exposure. , 2003, Advances in space research : the official journal of the Committee on Space Research.

[8]  M. Wyss,et al.  Creatine and creatinine metabolism. , 2000, Physiological reviews.

[9]  J. Fike,et al.  High-LET Radiation Induces Inflammation and Persistent Changes in Markers of Hippocampal Neurogenesis , 2005, Radiation research.

[10]  J. Coyle,et al.  Endogenous N‐acetylaspartylglutamate reduced NMDA receptor‐dependent current neurotransmission in the CA1 area of the hippocampus 1 , 2007, Journal of neurochemistry.

[11]  P. Valk,et al.  MRI and PET of delayed heavy-ion radiation injury in the rabbit brain. , 1991, International journal of radiation oncology, biology, physics.

[12]  B. Shukitt-Hale,et al.  Spatial Learning and Memory Deficits Induced by Exposure to Iron-56-Particle Radiation , 2000, Radiation research.

[13]  J. Moffett,et al.  N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology , 2007, Progress in Neurobiology.

[14]  A. Obenaus,et al.  Neuronal and glial cell populations in the piriform cortex distinguished by using an approximation of q-space imaging after status epilepticus. , 2004, AJNR. American journal of neuroradiology.

[15]  L Verhey,et al.  Serial proton MR spectroscopic imaging of recurrent malignant gliomas after gamma knife radiosurgery. , 2001, AJNR. American journal of neuroradiology.

[16]  A. le Pape,et al.  Experimental MR study of cerebral radiation injury: quantitative T2 changes over time and histopathologic correlation. , 1995, AJNR. American journal of neuroradiology.

[17]  Kortaro Tanaka,et al.  Enhanced Expression of Iba1, Ionized Calcium-Binding Adapter Molecule 1, After Transient Focal Cerebral Ischemia In Rat Brain , 2001, Stroke.

[18]  A. le Pape,et al.  Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain. , 1995, International journal of radiation oncology, biology, physics.

[19]  Boxer,et al.  An Animal Model , 2005 .

[20]  Markku Penttonen,et al.  Quantitative Assessment of the Balance between Oxygen Delivery and Consumption in the Rat Brain after Transient Ischemia with T2-BOLD Magnetic Resonance Imaging , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  Y. Fukuuchi,et al.  Microglia-specific localisation of a novel calcium binding protein, Iba1. , 1998, Brain research. Molecular brain research.

[22]  A. Obenaus,et al.  Cortical devascularization: quantitative diffusion weighted magnetic resonance imaging and histological findings , 2001, Brain Research.

[23]  Jacob Raber,et al.  Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis , 2004, Radiation research.

[24]  D. Nelson,et al.  Disruption of the blood-brain barrier as the primary effect of CNS irradiation. , 1994, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  S. Leung,et al.  Proton magnetic resonance spectroscopy of late delayed radiation‐induced injury of the brain , 1999, Journal of magnetic resonance imaging : JMRI.

[26]  J. Walecki,et al.  1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas. , 2002, International journal of radiation oncology, biology, physics.

[27]  R. Kauppinen,et al.  Graded Reduction of Cerebral Blood Flow in Rat as Detected by the Nuclear Magnetic Resonance Relaxation Time T2: A Theoretical and Experimental Approach , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  Soo Yeol Lee,et al.  Ex vivo proton MR spectroscopy (1H-MRS) for evaluation of human gastric carcinoma. , 2004, Magnetic resonance imaging.

[29]  S. Nelson,et al.  Serial evaluation of patients with brain tumors using volume MRI and 3D 1H MRSI , 1999, NMR in biomedicine.

[30]  L. Vargova,et al.  Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia , 1996, Magnetic resonance in medicine.

[31]  J. Fike,et al.  The Radioresponse of the Central Nervous System: A Dynamic Process , 2000, Radiation research.

[32]  D Le Bihan,et al.  Is water diffusion restricted in human brain white matter? An echo-planar NMR imaging study. , 1993, Neuroreport.

[33]  S. Vandenberg,et al.  Indicators of Hippocampal Neurogenesis are Altered by 56Fe-Particle Irradiation in a Dose-Dependent Manner , 2004, Radiation research.

[34]  H. B. Verheul,et al.  Comparison of diffusion‐weighted MRI with changes in cell volume in a rat model of brain injury , 1994, NMR in biomedicine.

[35]  B. Shukitt-Hale,et al.  Brain Signaling and Behavioral Responses Induced by Exposure to 56Fe-Particle Radiation , 2002, Radiation research.

[36]  M. Monje,et al.  Irradiation induces neural precursor-cell dysfunction , 2002, Nature Medicine.

[37]  J. Tsuruda,et al.  Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. , 1990, Radiology.

[38]  Thomas Krucker,et al.  Effects of Lipopolysaccharide on 56Fe-Particle Radiation-Induced Impairment of Synaptic Plasticity in the Mouse Hippocampus , 2007, Radiation research.

[39]  1H-MR spectroscopy of normal brain tissue before and after postoperative radiotherapy because of primary brain tumors. , 2003, International journal of radiation oncology, biology, physics.

[40]  C. J. Wall,et al.  Rapid alterations in diffusion-weighted images with anatomic correlates in a rodent model of status epilepticus. , 2000, AJNR. American journal of neuroradiology.