A stereotactic method for the three‐dimensional registration of multi‐modality biologic images in animals: NMR, PET, histology, and autoradiography

Abstract

The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.

Comprehensive Approach to Coregistration of Autoradiography and Microscopy Images Acquired from a Set of Sequential Tissue Sections

“…Nevertheless, intermodality image registration cannot rely on image content, as to avoid alignment of regions that have similar content but are not biologically colocalized. Landmarkbased registration remains the most objective registration method for multimodality imaging (7).…”

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration

“…In the past two decades, there have also been many studies specifically dealing with in-vivo brain MRI to post-mortem histology. The majority of these studies focused on primates (Dauguet et al, 2007;Malandain et al, 2004;Breen et al, 2005;Ceritoglu et al, 2010;Choe et al, 2011) or rodents (Jacobs et al, 1999;Humm et al, 2003;Meyer et al, 2006;Lebenberg et al, 2010;Yang et al, 2012;Liu et al, 2012). The few studies that registered human brain MRIto histology were performed on wholebrain (Schormann et al, 1995;Kim et al, 2000;Singh et al, 2008), or single hemisphere (Yelnik et al, 2007;Osechinskiy and Kruggel, 2011) post-mortem serially sectioned data (Amunts et al, 2013) created a 3D model of single subject's brain using post-mortem histological sections reconstructed at 20 m isotropic resolution and registered it to a T1 average atlas created from 24 subjects.…”

Immobilization using dental material casts facilitates accurate serial and multimodality small animal imaging

“…In an earlier study, Humm et al demonstrated an elegant registration procedure where fiducials were embedded into the tissue. Submillimeter registration accuracy was reported (2). In describing the method to transform magnetic resonance imaging (MRI) coordinates to tissue sections for histology, they showed a figure with the tissue embedded in optimal cutting tissue cryofixative.…”