Histological Validation of MRI: A Review of Challenges in Registration of Imaging and Whole-Mount Histopathology.

Rigorous validation with ground truth information such as histology is needed to reliably assess the current and potential value of MRI techniques to characterize tissue and identify disease-related tissue alterations. Commonly used methods that aim to directly correlate histology and MRI data generally fall short of this goal due to spatial errors that preclude direct matching. Errors result from tissue deformation, differences in spatial resolution and slice thickness, non-coplanar and/or nonintersecting plane orientations, and different image contrast mechanisms. Some of these problems arise from limitations in standard protocols for clinical tissue processing and histology-based pathology reporting, and to some extent can be addressed by modifications to standard protocols without compromising the clinical process. Typical modifications include ex vivo specimen MRI, block-face photography, addition of fiducial markers, and 3D printed molds to constrain tissue deformation and guide sectioning. This review summarizes the advantages and limitations of MRI validation techniques based on coregistration of MRI with whole-mount histology of tissue specimens. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).

Two [(18)F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[(18)F]fluoro-2-methylheptanoic acid ((S)-[(18)F]FAMHep, (S)-[(18)F]14) and (S)-2-amino-7-[(18)F]fluoroheptanoic acid ((S)-[(18)F]FAHep, (S)-[(18)F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[(18)F]15 but not (S)-[(18)F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[(18)F]15 in normal brain. (S)-[(18)F]15 had imaging properties similar to those of (S)-[(18)F]FET in the DBT tumor model while (S)-[(18)F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.