To the best of the authors’ knowledge, this is the first in-vitro study describing the imaging characteristics of xanthine stones on CT with multiple different energy levels, US and MRI. A previous in-vivo study of xanthine stones using conventional single energy CT showed CT numbers of stones ranging from 276–480 HU [2]. Previous in-vivo US studies have shown xanthine stones to be echogenic with posterior acoustic shadowing, with features identical to other urinary calculi [3]. No previous studies have described the imaging characteristics of xanthine stones on MRI.
On the four different energy levels on CT, xanthine stones had an average CT number of 321.4–331.0 HU, which is similar to CT numbers reported in a previous in vivo study of xanthine stones that used conventional single energy CT. There was no significant difference in the measured HU when imaging at different energies (80, 100, 120 and 140 kVp).
Interestingly, xanthine stones have relatively lower CT numbers than most urinary calculi. For example, reported mean CT numbers for struvite stones are 401–871 HU, cystine stones are 248–1088 HU, calcium oxalate stones are 865–1039 HU, and calcium phosphate stones are 1417 HU [6–8]. Xanthine stones have similar mean CT numbers to uric acid stones, which have reported CT numbers ranging from 270–519 [6, 8]. This may not be surprising given that xanthine and uric acid are part of the same metabolic pathway. The lower density of xanthine stones likely explains the previous literature describing them as radiolucent on radiographs. The lower density makes them more difficult to appreciate on radiographs than other more dense calculi, and stones were likely radiographically occult rather than truly radiolucent.
On US, all xanthine stones were echogenic, showed posterior acoustic shadowing, and demonstrated twinkle artifact with color Doppler imaging. These features are identical to other types of urinary stones. Previous in-vivo analyses of xanthine stones have also showed them to be indistinguishable from other urinary stones on US [1–3]. Based on these findings, ultrasound is equally suitable to evaluate xanthine stones as any other type of urinary stone.
Xanthine stones showed no signal on all MRI sequences tested, including UTE MRI sequences. Stones are expected to result in signal voids on conventional MRI sequences, but recent studies of UTE imaging have shown signal within other types of urinary calculi on UTE sequences [9, 10]. This has led some to suggest that these sequences might be utilized to evaluate urolithiasis. Our analysis suggests that xanthine stones are unlikely to be well visualized when utilizing the described MRI techniques in a clinical setting, including UTE sequences.
Although xanthine urolithiasis is a rare condition, it may cause recurrent symptoms in patients with Lesch-Nyhan Syndrome on allopurinol therapy and in patients with hereditary xanthinuria. Children with Lesch-Nyhan Syndrome are developmentally delayed and are often unable to appropriately verbalize their symptoms, making imaging particularly important in the clinical assessment of these patients. Given the recurrent nature of this condition, multiple imaging studies may be needed over the course of a lifetime. Based on the results of this in-vitro study, xanthine stones are easily detectable on US. Therefore, US should be the first line imaging test in the evaluation of xanthine stones given its lack of ionizing radiation and ability to visualize these stones. Recent developments in UTE MRI sequences have suggested that MRI may provide an additional imaging modality to assess urinary caluli without ionizing radiation. However, our analysis suggests that xanthine stones are not easily detectable on MRI, including UTE sequences, and MRI is unlikely to be helpful in the evaluation of xanthine urolithiasis. Our analysis suggests that xanthine stones are well visualized on CT. Therefore, judicious use of conventional single energy non-contrast CT may be appropriate in patients with xanthine urolithiasis when ultrasound is inconclusive or insufficient. The risks of radiation exposure should always be considered, especially given the recurrent nature of this condition and the potential need for multiple imaging studies over a lifetime.
A limitation of our study stems from the small size of xanthine stones studied. Stones smaller than 5 mm in diameter tend to demonstrate lower CT numbers regardless of composition secondary to partial-volume effects. CT numbers in our analysis may be lower given the smaller size of the stones studied. Previous MRI studies that were able to demonstrate signal within urinary stones used stones larger than 1 cm, which is larger than the stones evaluated in this study [7, 10, 11]. This small size may have contributed to the lack of signal seen on all MRI sequences tested in our study. Future studies could benefit from analyzing larger stones, if available.