Micro-CT for Anatomic Referencing in PET and SPECT: Radiation Dose, Biologic Damage, and Image Quality

Abstract

CT is widely used for anatomic referencing of PET and SPECT images of small animals but requires sufficiently high radiation doses capable of causing significant DNA damage. Therefore, we described the relationship between radiation dose, biologic damage, and image quality to determine whether CT can be used without significantly compromising radiotherapy and tumor development studies. Methods: The CT dose index generated by the nanoSPECT/CT system was compared with measurements using EBT2 gafchromic film. The effects of micro-CT were evaluated in 2 mouse strains that differ in sensitivity to radiation. gH2AX foci analysis to determine leukocyte, liver, and jejunum DNA damage and hematoxylin and eosin staining to investigate macroscopic jejunum damage were performed. Signal-to-noise ratio, contrast-to-noise ratio, and scanner linearity were determined to assess image quality. Results: For the standard settings, that is, as set by the manufacturers, EBT2 gafchromic film dosimetry showed that the nanoSPECT/ CT system underestimated the absorbed dose. Moreover, significant doses were obtained, resulting in a significant increase in gH2AX formation in leukocytes, liver, and jejunum 40 min after CT, using preset parameters when compared with nonimaged controls. The jejenum response was more pronounced for the more radiosensitive strain. In contrast to leukocytes, the liver and jejunum still showed evidence of DNA damage 3 d after CT. Contrast-to-noise ratio, signal-to-noise ratio, and scanner linearity were sufficient to allow for anatomic referencing for both imaging protocols tested. Conclusion: Anatomic reference images can be produced with no observable DNA damage or compromising image quality using low radiographic voltage, flux, and duration.

High Dose MicroCT Does Not Contribute Toward Improved MicroPET/CT Image Quantitative Accuracy and Can Limit Longitudinal Scanning of Small Animals

“…Notwithstanding, the impact high dose CT has on longitudinal experimental results remains controversial. Studies often report opposing findings from no effects regarding dose delivered to tumors during longitudinal studies to results indicating high doses can induce tumor inhibition [19,20,[34][35][36]. Using a Mediso nanoPET/CT scanner, we found that for both the air/water and the TEM phantoms, decreasing CT dose resulted in visual image quality degradation and high noise, but had a relatively minimal impact on HU quantification, while adversely increasing small animal absorbed dose.…”

“…Conversely, the majority of studies addressing microPET/CT optimization of protocols have been performed primarily using the manufacturers default protocol or slight variations thereof [18,19]. Therefore, the impact of varying microCT parameters on microPET/CT data and preclinical research results is poorly defined and not fully understood.…”

Performance Evaluation and X-ray Dose Quantification for Various Scanning Protocols of the GE eXplore 120 Micro-CT

“…Hupfer [15], using a TomoScope microCT (CT Imaging GmbH, Erlangen, Germany), reported a inside a 32-mm cylindrical phantom of approximately 2.2 mGy/mAs (40 kV, 23 mAs). Kersemans [6], using a Bioscan nanoSPECT/CT, measured a CTDI inside a 60-mm-diameter cylindric PMMA phantom of 7.7 mGy/mAs (35 kV, 50 A, 400 ms, 180 projections) to 3.7 mGy/mAs (65 kV, 123 A, 2 s, and 360 projections). When comparing literature values of dose output, it should be noted that the size of the phantom as well as the material have an impact on the measurement.…”

“…In order to reach the high resolution (typically 50-100 m) needed when imaging small animals, the X-ray dose delivered must be high compared to clinical scanners in order to improve signal-to-noise ratio, which is achieved by increasing the tube current and the exposure time per projection [3]. Since longitudinal studies, often combined with other ionizing imaging modalities like positron emission tomography or single photon emission tomography, are increasingly used in preclinical imaging [4], [5], it is important to quantify the radiation delivered to the animals to rule out any influence of the irradiation on the outcome of the study [6]. A dose of 6 Gy is considered lethal to a mouse [7], however some studies report that even low doses can affect protein expressions [8] and alter signal transduction of neurons in mouse hypothalamus [9].…”

LabPET II, an APD-based Detector Module with PET and Counting CT Imaging Capabilities

“…In vivo PET imaging of small animals, being a useful molecular imaging tool, also benefits from overlaying molecular and functional information on an anatomical support [4]. However, PET is often used on its own in preclinical studies in order to avoid or partially reduce the high radiation dose from CT imaging, which may lead to undesired therapeutic effects especially in longitudinal studies [5]- [8]. Moreover, scaling from humans ( kg) to mice ( g) pushes the detectors and electronics to their limits, as very high spatial resolution is required [9].…”