Evaluation of registration strategies for multi-modality images of rat brain slices

In neuroscience, small-animal studies frequently involve dealing with series of images from multiple modalities such as histology and autoradiography. The consistent and bias-free restacking of multi-modality image series is obligatory as a starting point for subsequent non-rigid registration procedures and for quantitative comparisons with positron emission tomography (PET) and other in vivo data. Up to now, consistency between 2D slices without cross validation using an inherent 3D modality is frequently presumed to be close to the true morphology due to the smooth appearance of the contours of anatomical structures. However, in multi-modality stacks consistency is difficult to assess. In this work, consistency is defined in terms of smoothness of neighboring slices within a single modality and between different modalities. Registration bias denotes the distortion of the registered stack in comparison to the true 3D morphology and shape. Based on these metrics, different restacking strategies of multi-modality rat brain slices are experimentally evaluated. Experiments based on MRI-simulated and real dual-tracer autoradiograms reveal a clear bias of the restacked volume despite quantitatively high consistency and qualitatively smooth brain structures. However, different registration strategies yield different inter-consistency metrics. If no genuine 3D modality is available, the use of the so-called SOP (slice-order preferred) or MOSOP (modality-and-slice-order preferred) strategy is recommended

Quantifying the A1AR distribution in peritumoral zones around experimental F98 and C6 rat brain tumours

Quantification of growth in experimental F98 and C6 rat brain tumours was performed on 51 rat brains, 17 of which have been further assessed by 3D tumour reconstruction. Brains were cryosliced and radio-labelled with a ligand of the peripheral type benzodiazepine-receptor (pBR), (3)H-Pk11195 [(1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propylene)-3-isoquinoline-carboxamide)] by receptor autoradiography. Manually segmented and automatically registered tumours have been 3D-reconstructed for volumetric comparison on the basis of (3)H-Pk11195-based tumour recognition. Furthermore automatically computed areas of -300 microm inner (marginal) zone as well as 300 microm and 600 microm outer tumour space were quantified. These three different regions were transferred onto other adjacent slices that had been labelled by receptor autoradiography with the A(1) Adenosine receptor (A(1)AR)-ligand (3)H-CPFPX ((3)H-8-cyclopentyl-3-(3-fluorpropyl)-1-propylxanthine) for quantitative assessment of A(1)AR in the three different tumour zones. Hence, a method is described for quantifying various receptor protein systems in the tumour as well as in the marginal invasive zones around experimentally implanted rat brain tumours and their representation in the tumour microenvironment as well as in 3D space. Furthermore, a tool for automatically reading out radio-labelled rat brain slices from auto radiographic films was developed, reconstructed into a consistent 3D-tumour model and the zones around the tumour were visualized. A(1)AR expression was found to depend upon the tumour volume in C6 animals, but is independent on the time of tumour development. In F98 animals, a significant increase in A(1)AR receptor protein was found in the Peritumoural zone as a function of time of tumour development and tumour volume