Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging

Augustinack, Jean C.; Helmer, Karl G.; Huber, Kristen E.; Kakunoori, Sita; Zöllei, Lilla; Fischl, Bruce

doi:10.3389/fnhum.2010.00042

Cited by 76 publications

(91 citation statements)

References 67 publications

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“…This analysis was performed by C.T.F., an MR imaging physicist with 12 years of experience with MR imaging, CEST, and imaging of tumor models. The mean CEST image contrast in the tumor ROI was normalized according to the contralateral hemisphere to remove asymmetric magnetization transfer effects and to provide an objective ROI for normalization of the tumor CEST image contrast (19,20). The normalized tumor CEST image contrast is defined as tumor contralateral asym asym (MTR -MTR ).…”

Section: Molecular Imaging: Lysine-rich Protein Chemical Exchange Satmentioning

confidence: 99%

Establishing the Lysine-rich Protein CEST Reporter Gene as a CEST MR Imaging Detector for Oncolytic Virotherapy

Farrar¹,

Buhrman²,

Liu³

et al. 2015

Radiology

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Purpose:To (a) evaluate whether the lysine-rich protein (LRP) magnetic resonance (MR) imaging reporter gene can be engineered into G47D, a herpes simplex-derived oncolytic virus that is currently being tested in clinical trials, without disrupting its therapeutic effectiveness and (b) establish the ability of chemical exchange saturation transfer (CEST) MR imaging to demonstrate G47D-LRP. Materials and Methods:The institutional subcommittee for research animal care approved all in vivo procedures. Oncolytic herpes simplex virus G47D, which carried the LRP gene, was constructed and tested for its capacity to replicate in cancer cells and express LRP in vitro. The LRP gene was detected through CEST imaging of lysates derived from cells infected with G47D-LRP or the control G47D-empty virus. G47D-LRP was then tested for its therapeutic effectiveness and detection with CEST MR imaging in vivo. Images of rat gliomas were acquired before and 8-10 hours after injection of G47D-LRP (n = 7) or G47D-empty virus (n = 6). Group comparisons were analyzed with a paired t test. Results:No significant differences were observed in viral replication or therapeutic effectiveness between G47D-LRP and G47D-empty virus. An increase in CEST image contrast was observed in cell lysates (mean 6 standard deviation, 0.52% 6 0.06; P = .01) and in tumors (1.1% 6 0.3, P = .02) after infection with G47D-LRP but not G47D-empty viruses. No histopathologic differences were observed between tumors infected with G47D-LRP and G47D-empty virus. Conclusion:This study has demonstrated the ability of CEST MR imaging to show G47D-LRP at acute stages of viral infection. The introduction of the LRP transgene had no effect on the viral replication or therapeutic effectiveness. This can aid in development of the LRP gene as a reporter for the real-time detection of viral spread.q RSNA, 2015

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Section: Molecular Imaging: Lysine-rich Protein Chemical Exchange Satmentioning

confidence: 99%

Establishing the Lysine-rich Protein CEST Reporter Gene as a CEST MR Imaging Detector for Oncolytic Virotherapy

Farrar¹,

Buhrman²,

Liu³

et al. 2015

Radiology

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“…Differences between rats and human in hippocampal anatomy and connectivity with the perforant pathway (Augustinack et al, 2010;Lehmann et al, 2000;van Groen et al, 2002;Witter et al, 2000) may contribute to the development of divergent phenotypes.…”

Section: Comparison To Previous Studies For Gs Quantification In Epilmentioning

confidence: 99%

Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats

Papageorgiou

Gabriel

Fetani

et al. 2011

Glia

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Glutamine synthetase (GS) is an astrocytic enzyme, which catalyzes the synthesis of glutamine from glutamate and ammonia. In the central nervous system, GS prevents glutamate-dependent excitotoxicity and detoxifies nitrogen. Reduction in both expression and activity of GS was reported in the hippocampus of patients with temporal lobe epilepsy (TLE), and this reduction has been suggested to contribute to epileptogenesis. In this study, we characterized hippocampal GS expression in the pilocarpine model of TLE in Wistar rats by means of stereology and morphometric analysis. Neither the GS positive cell number nor the GS containing cell volume was found to be altered in different hippocampal subregions of chronic epileptic rats when compared with controls. Instead, redistribution of the enzyme at both intracellular and tissue levels was observed in the epileptic hippocampus; GS was expressed more in proximal astrocytic branches, and GS expressing astrocytic somata was located in closer proximity to vascular walls. These effects were not due to shrinkage of astrocytic processes, as revealed by glial fibrillary acidic protein staining. Our results argue for GS redistribution rather than downregulation in the rat pilocarpine model of TLE. The potential contribution of increased GS perivascular affinity to the pathogenesis of epilepsy is discussed as well.

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“…A critical connection for normal hippocampal function is the perforant pathway (PP), as depicted in Figure 1 (Augustinack et al, 2010;Stark, 2007;Zola-Morgan and Squire, 1993). For memory consolidation in the healthy brain, incoming sensory information from visual, auditory, and somatic association cortices converges in the mesocortical regions and projects to the dentate gyrus granule cells and hippocampal pyramidal neurons via the PP.…”

Section: Introductionmentioning

confidence: 99%

“…For memory consolidation in the healthy brain, incoming sensory information from visual, auditory, and somatic association cortices converges in the mesocortical regions and projects to the dentate gyrus granule cells and hippocampal pyramidal neurons via the PP. This polysynaptic intrahippocampal pathway includes a long neuronal chain that is composed of the entorhinal area, the dentate gyrus, the cornu ammonis (CA3 and CA1), and the subiculum (for detailed description, see Augustinack et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Diffusion Tensor Imaging of the Perforant Pathway Zone and Its Relation to Memory Function in Patients with Severe Traumatic Brain Injury

Christidi

Bigler

McCauley

et al. 2011

Journal of Neurotrauma

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Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.

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Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging

Cited by 76 publications

References 67 publications

Establishing the Lysine-rich Protein CEST Reporter Gene as a CEST MR Imaging Detector for Oncolytic Virotherapy

Establishing the Lysine-rich Protein CEST Reporter Gene as a CEST MR Imaging Detector for Oncolytic Virotherapy

Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats

Diffusion Tensor Imaging of the Perforant Pathway Zone and Its Relation to Memory Function in Patients with Severe Traumatic Brain Injury

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