Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain.

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.

Single chain ferritin chimera as an improved MRI gene reporter.

Imaging gene expression non-invasively and deep into opaque tissues has been a long-standing goal of molecular science. Optical gene reporters such as green fluorescent protein and luciferase have revolutionized cellular and molecular biology, however their in vivo application is limited, due to poor tissue penetration of visible light. The iron storage protein ferritin forms a paramagnetic ferrihydrite core that affects the relaxation rate of surrounding nuclear spins. Ferritin has recently emerged as an MRI gene reporter for molecular applications, however its detection with MRI still has relatively low sensitivity. In this work we present an improved ferritin chimera, genetically engineered to exhibit stronger paramagnetic properties.

MR imaging anatomy in neurodegeneration: a robust volumetric parcellation method of the frontal lobe gyri with quantitative validation in patients with dementia.

BACKGROUND AND PURPOSE: Brain volumetry is widely used for evaluating tissue degeneration; however, the parcellation methods are rarely validated and use arbitrary planes to mark boundaries of brain regions. The goal of this study was to develop, validate, and apply an MR imaging tracing method for the parcellation of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to the structures of interest, without the need for global reorientation or the use of dividing planes or lines. METHODS: Studies were performed on 25 subjects--healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer disease--with significant variation in the underlying gyral anatomy and state of atrophy. The protocol was evaluated by using multiple observers tracing scans of subjects diagnosed with neurodegenerative disease and those aging normally, and the results were compared by spatial overlap agreement. To confirm the results, observers marked the same locations in different brains. We illustrated the variabilities of the key boundaries that pose the greatest challenge to defining consistent parcellations across subjects. RESULTS: The resulting gyral volumes were evaluated, and their consistency across raters was used as an additional assessment of the validity of our marking method. The agreement on a scale of 0-1 was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85 spatial and 0.90 volumetric for 2 different raters. The results revealed that the protocol remained consistent across different neurodegenerative conditions. CONCLUSION: Our method provides a simple and reliable way for the volumetric evaluation of frontal lobe neurodegeneration and can be used as a resource for larger comparative studies as well as a validation procedure of automated algorithms.

A novel approach to high resolution fetal brain MR imaging.

This paper describes a novel approach to forming high resolution MR images of the human fetal brain. It addresses the key problem of motion of the fetus by proposing a registration refined compounding of multiple sets of orthogonal fast 2D MRI slices, that are currently acquired for clinical studies, into a single high resolution MRI volume. A robust multi-resolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between 2D acquisitions. This is combined with an intensity correction step and a super resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions are included. Results indicate the method promises a unique route to acquiring high resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data is highly valuable in allowing a clinically applicable window into the process of normal and abnormal brain development.