High-throughput multiple-mouse imaging with micro-PET/CT for whole-skeleton assessment

Abstract

Recent studies have proven that skeleton-wide functional assessment is essential to comprehensively understand physiological aspects of the skeletal system. Therefore, in contrast to regional imaging studies utilizing a multiple-animal holder (mouse hotel), we attempted to develop and characterize a multiple-mouse imaging system with micro-PET/CT for high-throughput whole-skeleton assessment. Using items found in a laboratory, a simple mouse hotel that houses four mice linked with gas anesthesia was constructed. A mouse-simulating phantom was used to measure uniformity in a cross sectional area and flatness (Amax/Amin*100) along the axial, radial and tangential directions, where Amax and Amin are maximum and minimum activity concentration in the profile, respectively. Fourteen mice were used for single- or multiple-micro-PET/CT scans. NaF uptake was measured at eight skeletal sites (skull to tibia). Skeletal 18F activities measured with mice in the mouse hotel were within 1.6±4% (mean±standard deviation) of those measured with mice in the single-mouse holder. Single-holder scanning yields slightly better uniformity and flatness over the hotel. Compared to use of the single-mouse holder, scanning with the mouse hotel reduced study time (by 65%), decreased the number of scans (four-fold), reduced cost, required less computer storage space (40%), and maximized 18F usage. The mouse hotel allows high-throughput, quantitatively equivalent scanning compared to the single-mouse holder for micro-PET/CT imaging for whole-skeleton assessment of mice.

High-Throughput PET/CT Imaging Using a Multiple-Mouse Imaging System

“…The feasibility of simultaneously imaging more than one animal in the same PET/CT system has been reported for multiple studies (8)(9)(10)12), facilitated through the development of new small-animal PET/CT platforms that offer sensitive and reproducible imaging over both a large axial and a large transaxial field of view. To the best of our knowledge, however, physiologic regulation and monitoring have not been incorporated into the user-developed animal holders currently in existence.…”

“…A potential solution to this economic problem is to scan multiple animals simultaneously. Several commercially available preclinical scanners have adequate axial length and diameter to achieve multianimal imaging, and as a result, many user-designed multianimal holders have entered routine application (8)(9)(10). Often, however, these beds lack the thorough characterization required for the production of reproducible and quantifiable PET data, with animal heating and monitoring capabilities frequently omitted from the bed design.…”

High Throughput PET/CT Imaging Using a Multiple Mouse Imaging System

“…The feasibility of imaging multiple animals in the same small animal PET/CT imaging system has been reported in multiple studies (8)(9)(10)12) including disruption to thermoregulation, respiration and cardiac output (13). Maintaining a constant bed temperature will therefore limit variations in radiotracer pharmacokinetics, whilst minimizing any potential pain, suffering, distress or lasting harm that may be caused to the animal.…”

“…A potential solution to this economic problem is to scan multiple animals simultaneously. A number of commerciallyavailable preclinical scanners possess adequate axial length and diameter to achieve multianimal imaging, and as a result, many user-designed multi-animal holders have entered into routine use (8)(9)(10). Often, however, these beds lack the thorough characterization required for the production of reproducible and quantifiable PET data, with animal heating and monitoring capabilities frequently omitted from the bed design.…”

Early assessment of dosimetric and biological differences of total marrow irradiation versus total body irradiation in rodents

“…Tissues were fixed, embedded in paraffin and evaluated semi-quantitatively for histological changes [11]. Tissue metabolic damage was evaluated in a subset of mice using longitudinal fluorodeoxyglucose (FDG) micro-PET/CT imaging following the method described previously [12, 13]. …”