A retrospective study of SPECT/CT scans using SUV measurement of the normal pelvis with Tc-99m methylene diphosphonate

Currently the most commonly used tracer for imaging the skeleton in conventional nuclear medicine is technetium99m-labeled methylene diphosphonate (99mTc-MDP) bone scintigraphy, which is a cost-effective and useful tool and has variable diagnostic sensitivity with comparatively low specifi city [1]. Bone scintigraphy is the standard of reference in bone metastases in cancer patients. The most common primary sites for bone metastases are lung, breast, prostate, kidney, and thyroid. The axial skeleton and the pelvis are the most common metastasis locations [2-7]. 99m Tc-MDP and hydroxymethylene diphosphonate have been widely used for bone scintigraphy [8]. Single-photon emission tomography (SPECT)/computed tomography (CT) scanner provides fusion images of CT and SPECT and also produces attenuation correction maps and directly correlated bone scan fi ndings with anatomic structures [9,10].


Introduction
Currently the most commonly used tracer for imaging the skeleton in conventional nuclear medicine is technetium-99m-labeled methylene diphosphonate ( 99m Tc-MDP) bone scintigraphy, which is a cost-effective and useful tool and has variable diagnostic sensitivity with comparatively low specifi city [1]. Bone scintigraphy is the standard of reference in bone metastases in cancer patients. The most common primary sites for bone metastases are lung, breast, prostate, kidney, and thyroid. The axial skeleton and the pelvis are the most common metastasis locations [2][3][4][5][6][7]. 99m Tc-MDP and hydroxymethylene diphosphonate have been widely used for bone scintigraphy [8]. Single-photon emission tomography (SPECT)/computed tomography (CT) scanner provides fusion images of CT and SPECT and also produces attenuation correction maps and directly correlated bone scan fi ndings with anatomic structures [9,10].
Quantitative measurements have become vastly important with advances in molecular imaging. Sullivan developed various quantitative imaging biomarkers (QIBs). However, few of these QIBs are used routinely in clinical trials or clinical care [11,12]. Quantitative analyses have been performed for bone scans of vertebrae using the standardized uptake value (SUV) as QIB of SPECT/CT scans with 99m Tc-MDP [8,13]. SUV is defi ned as the tissue concentration of tracer as measured by a positron emission tomography (PET) scanner divided by the activity concentration injected divided usually by body weight [8,14,15]. The uptake value is represented by pixel or voxel intensity value in the region of interest (ROI) of the image, which is then converted into the activity concentration. SUVs methylene diphosphonate. Int J Radiol Radiat Oncol 4(1): 003-008. DOI: http://dx.doi.org/10.17352/ijrro.000027 represent tissue activity within an ROI corrected for injected activity and body weight [16].
The pelvis in the most common localization after spine in bone metastasis [3]. The detection of occult bone metastases is a key factor in determining the management of patients with cancer, which can greatly alter patient management [13]. 99m Tc-MDP bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone [17], it was diffi cult to identify bone metastases in the early stages by visual evaluation. Thus, it is important to address the question of quantitative evaluation of hot spots in the pelvic bone. However, few reports have been published on SUV measurement as QIB in bone imaging using SPECT/CT scans with 99m Tc-MDP. The primary aim of this study was to report the SUV of the normal pelvis with absolute values, deviation, and variability. Furthermore, the correlations of SUVmax, SUVmean with height, weight, and CT were determined.

Patients
In this study, all patients were examined for staging malignancy, such as prostate cancer, pancreatic cancer, breast cancer, colon cancer, renal cancer, lung cancer, gastric cancer, and ovarian cancer. The data of patients with normal pelvis who underwent bone scans were retrospectively analyzed. Patient data analysis was carried out with permission from the Ethics Committee of the Affi liated Hospital of Shaanxi University of Chinese Medicine. Data were required for a group of 31 patients (20 women and 11 men) undergoing Tc-99m MDP (Atomic High-tech Co. Ltd, Beijing, China) bone SPECT/CT between August and December 2016.
The patients were included based on the following criteria: (1) access to data on measured injection activity, time of measurement, and time of injection; (2) access to patient's weight and height information; (3) SPECT/CT scans for pelvis; and (4) absence of diffuse bone metastases, ankylosing spondylitis, metabolic bone disease, and osteoarthritis.

Data acquisition and reconstruction
The measurements of system sensitivity, which vary depending on the radionuclide, thickness of the scintillation crystal, collimator, and pulse height analyzer energy windows used [18]. The Symbia T16 (CT with a maximum of 16 slice acquisitions per rotation, Siemens Healthcare, Molecular Imaging, IL, USA) system was used for SPECT/CT scans. The SPECT/CT scans with 3/8 inch NaI(Tl) detector and lowenergy, high resolution collimator were acquired, a 128 × 128 matrix of 4.8-mm pixel size, and a total of 450 s/rotation in a continuous-rotation mode. The pulse height analyzer energy windows were 140Kev±15%. Subsequent to the SPECT acquisition, a low-dose CT scan was acquired with 130 kV and 15 ref mAs using adaptive dose modulation (CARE Dose 4D; Siemens Healthcare Molecular Imaging, IL, USA). The CT data were generated with a 1.5-mm slice thickness using a smooth reconstruction B70s kernel. SPECT reconstruction was performed using fi ltered back-projection, and attenuation correction was based on attenuation maps derived from the CT data fi ltered with the B70s kernel.
The patient's clinical data was acquired from the hospital's HIS database.

Data analysis
The WBS and SPECT/CT images were independently interpreted by two experienced nuclear medicine physicians and a diagnostic radiologist. In cases of discrepancy, the consensus was obtained by a joint reading. From the pelvis scanned, SUVs of 31 pelves were calculated for analyses based on the previously defi ned criteria [18]. The delineation of the volumes of interest (VOIs) was performed using a newly

Statistical analyses
The degree of dispersion of SUV max and SUV mean of the normal pelvis were evaluated using the coeffi cient of variation (CV).
The data was analyzed using normal distribution test. Only the continuous variables that satisfi ed the normal distribution were tested using t test. Differences in SUVs between male and female participants were tested using a paired two-sample t test assuming equal variation. The relationships of SUVs with weight, height, and CT values were evaluated with a Pearson's correlation analysis. P values less than 0.05 indicated signifi cant differences. All analyses were computed using SPSS16.0 (IBM, USA).  Among the 31 normal pelves for which SUVs were calculated, 1 ischial tuberosity of the normal pelvis was excluded for the following statistical analyses because ischial nodules were not included in the scan range of SPECT/CT (Table 1)

Differences between male and female participants
In this study, the average age (58.97 ± 9.12) of male and female participants was 62.55 ± 7.88 and 57.00 ± 9.34, respectively. No signifi cant differences were found between male and female participants with regard to the SUVmax and SUVmean (Figure 3).

Discussion
SPECT/CT scanners have given renewed impetus to produce quantitative SPECT data. The CT data complement the SPECT data, which can be used to correct for photons that have been Compton-scattered or attenuated within the body.
Also, algorithms for image reconstruction and sophisticated compensation techniques to correct for photon attenuation and scattering have made quantitative SPECT viable in a manner similar to quantitative PET (i.e., kBqcm -3 , SUV) [18,19]. reported that the SUVs of normal vertebrae showed moderate and signifi cant correlation with the height of the participants [8]. The VOI of vertebrae were seated over cancellous bone   Therefore, no signifi cant correlation was found between the SUVs and height and body weight of the participants.
In Tomohiro study, the mean age of male participants was about 5 years higher than that of female participants. SUVs of the males were higher than those of females, and the difference was signifi cant [8]. The result of the present study showed that the mean age of male participants was about 5 years higher than that of female participants, and the difference in SUVs SPECT/CT readily achieves accuracy for 99m Tc to within ±10% of the known concentration of the radiotracer in vivo. Quantifi cation with other radionuclides has also been introduced. It is benefi cial in some situations of longer radionuclide half-lives. It may better suit the biologic process under examination and the ability to perform multitracer studies using pulse height spectroscopy to separate different radiolabels.
The main limitation of the present study was its small sample size. Also, it was a retrospective study, and repeated measurements of intraindividual variability could not be performed. Using lean mass or body surface area to normalize the data might help reduce data variability. Modern SPECT systems use iterative reconstruction algorithms such as ordered subsets expectation maximization (OSEM), rather than FBP, We compare the effect of FBP and iterative reconstruction method on SUVs in the future. The diagnostic accuracy of range in the present study needs further verifi cation.

Conclusions
SUVs of the normal pelvis showed a relatively large variability. As a quantitative imaging biomarker, SUVs might require standardization with adequate reference data for the participants to minimize variability.