This study shows that in conditions of image reconstruction targeting a high level of image quality, high-speed recording from this whole-body 360° CZT-SPECT/CT system provides reliable and potentially helpful SUV measurements in patients with vertebral fractures and/or compaction.
However, the poorer spatial resolution of SPECT compared with PET, and resultant higher partial volume effect, is considered as a disadvantage for SUV measurement. In analysis of the present study, only one SPECT reconstruction series was utilized with parameters favoring contrast-to-noise ratio -i.e., cubic voxels of only 2.46 mm and partial volume correction - and also, with filtering -i.e., median and kernel filters and only 32 equivalent OSEM iterations. These reconstruction parameters were those considered to provide the best compromise between image quality and the accuracy of activity measurements - i.e. high foci detectability, even for a 0.6 mL sphere volume, and with significant SUVmax underestimation only for spheres ≤ 5.8 mL (Fig. 1).
SUVmax was preferred here to other SUV parameters such as SUV mean and SUV peak. SUV mean was difficult to use in the absence of any precise knowledge regarding limits of the diseased bone volumes and when applied to the entire bodies of vertebrae, its ability to separate fractured from intact vertebrae was lower than that of SUVmax (see supplemental Fig. 4). In addition, a 1 cm3 volume within which the SUV peak is commonly determined was too large, exceeding the thickness of several very flattened vertebrae and the volume of the smallest phantom sphere. Finally, the well-known confusing influence of noise level on the determination of SUVmax [23, 24] was minimized here, due to our choice of reconstruction parameters favoring the contrast-to-noise ratio of the SPECT images.
Overall, our phantom results agree with the conclusions achieved by previous comparable studies planned on more conventional gamma-cameras, regarding the acceptable accuracy of SPECT SUV measurements [25, 26], especially for volumes ≥ 10 mL  and when associated with CT-based methods enabling reduction in the partial volume effect [28–30]. It is of note however, that underestimation of SUVmax for spheres < 10 mL was no longer observed when utilizing alternative reconstruction parameters that favored spatial resolution to a greater extent (≥ 20 OSEM equivalent iterations, less image filtering), albeit at the cost of an increase in the noise level (results not shown).
However, the remaining partial volume effects, observed here for volumes smaller than 5 to 10 mL, constitute a limitation, considering that the diseased parts of certain compacted vertebrae may represent a smaller than 5 to 10 mL volume. Despite this limitation, however, consistent results were observed in our longitudinal study of patients with vertebral fractures and/or compactions, thereby reinforcing the potential usefulness of our method of SUV measurement. These results include the stability over time of the SUVmax from intact control reference vertebrae. The T1 vertebrae were chosen for this stability analysis because of their very low risk of osteoporotic fractures , and because they were visually intact on the SPECT/CT images of our all patients.
The results also demonstrate a dramatic decrease over time for the SUVmax from fractured vertebrae, as would be expected, although elevated SUVmax levels were still documented during a 7-month period (Fig. 3). Such persistence of elevated SUVmax over the longer-term is not surprising considering that a great proportion of bone scintigraphy remains visually abnormal even at one year after a vertebral compression fracture .
SUV were already proven helpful for documenting longitudinal changes with PET imaging and more recently with bone-SPECT [1–3]. However, to the best of our knowledge, the present study is the first to use SUV for analyzing longitudinal changes in the metabolism of bone fractures. The potential usefulness of SUV measurement in this setting is best illustrated in Fig. 3 by the easy identification of any increase in bone metabolism, corresponding to new compaction fractures involved in a vertebral fracture cascade, when serial SPECT images are displayed with the same SUV-based scaling. Furthermore, this assessment was obtained with recording times of only 12 to 15 minutes for the entire spine. This latter property is likely advantageous in patients for whom a prolonged supine position on the camera bed is difficult to endure due to their painful fractures.
An additional observation was that as many as 98% of the fractured vertebrae exhibited SUVmax > 7.5 in the 7-month period following the acute episode, whereas this was highly unusual in the reference intact T1 vertebrae with only 4% exhibiting SUVmax > 7.5. Therefore, it may be considered that an image scaling favoring the identification of bone structures reaching a > 7.5 SUV level is required to easily detect most bone fractures, and especially the oldest ones.
Until now, this image scaling has routinely been done in an empirical and subjective visual way, mainly based on the % of maximal voxel activity, with high reader variability being a difficulty for uniformity of SPECT diagnoses. Standardized SUV-based scaling would likely enhance bone SPECT analysis reproducibility by optimally standardizing readers’ diagnostic review. It might also alleviate the difficulties encountered when scaling images where bone lesions are very diffuse (i.e., a super scan) or have very high maximal activity levels. This point is illustrated in a supplemental Fig. 5 by the SPECT images from an actual clinical case where the diagnosis could be corrected with a secondary analysis, thanks to the application of an SUV-based scaling method.
In conclusion, the high-speed whole-body CZT-SPECT/CT system presented here, in association with an adapted SPECT reconstruction for bone scintigraphy images, provides high image-quality together with reliable SUV measurements, at least for structures with ≥ 5 to 10 mL volume. These SUV measurements may attest to the longitudinal changes in vertebral bone metabolism -i.e., SUV decrease during fracture healing and iSUV increase after a fracture recurrence and within a possible framework of cascade fractures. And further, more generally, these SUV measurements might also help to enhance the reproducibility and robustness of bone scintigraphy analyses.