Recent research showed that the attenuation can be determined from emission data, jointly with reconstructed activity images, up to a scaling constant when utilizing the time-of-flight (TOF) information. We aim to develop practical joint reconstruction for clinical TOF PET scanners with autonomous scaling determination and joint TOF scatter estimation from TOF PET data, to obtain quantitatively accurate activity and attenuation images. In this work, we present a joint reconstruction of activity and attenuation based on MLAA with autonomous scaling determination. Our idea is to use a segmented region in a reconstructed attenuation image with known attenuation, e.g., a liver in patient imaging. First, we construct a unit attenuation medium which has a similar, not necessarily the same, support to the imaging patient. All detectable LORs intersecting the unit media have an attenuation factor of e<sup>−1</sup> ≈ 0.3679, i.e., the line integral is one. The scaling factor can then be determined by comparing the reconstructed attenuation image and the unit attenuation medium within the segmented known region(s). A three-step iterative joint reconstruction algorithm is developed. In each iteration, first the activity is updated using TOF OSEM from TOF list-mode data; then the attenuation image is updated using XMLTR—a modified MLTR from non-TOF LOR sinograms; a scaling factor is determined based on the segmented region(s) and both activity and attenuation images are updated using the estimated scaling. We implement the joint reconstruction with autonomous scaling, and evaluate using 3-D simulations. The joint reconstructions are also compared with the reference reconstruction with true attenuation image. In summary, we present a joint reconstruction of activity and attenuation with autonomous scaling. The scaling determination at each iteration allows the joint reconstruction to obtain a unique and faithful solution of activity and attenuation.
We previously showed that optical redox imaging (ORI) of snap-frozen breast biopsies by the Chance redox scanner readily discriminates cancer from normal tissue. Moreover, indices of redox heterogeneity differentiate among tumor xenografts with different metastatic potential. These observations suggest that ORI of fluorescence of NADH and oxidized flavoproteins (Fp) may provide diagnostic/prognostic value for clinical applications. In this work, we investigate whether ORI of formalin-fixed-paraffin-embedded (FFPE) unstained clinical tissue slides of breast tumors is feasible and comparable to ORI of snap-frozen tumors. If ORI of FFPE is validated, it will enhance the versatility of ORI as a novel diagnostic/prognostic assay as FFPE samples are readily available. ORI of fixed tissue slides was performed using a fluorescence microscope equipped with a precision automated stage and appropriate optical filters. We developed a vignette correction algorithm to remove the tiling effect of stitched-images. The preliminary data from imaging fixed slides of breast tumor xenografts showed intratumor redox heterogeneity patterns similar to that of the frozen tissues imaged by the Chance redox scanner. From ORI of human breast tissue slides we identified certain redox differences among normal, ductal carcinoma in situ, and invasive carcinoma. We found paraformaldehyde fixation causes no change in NADH signals but enhances Fp signals of fresh muscle fibers. We also investigated the stability of the fluorescence microscope and reproducibility of tissue slide fluorescence signals. We plan to validate the diagnostic/prognostic value of ORI using clinically annotated breast cancer sample set from patients with long-term follow-up data.